Fatty acids tall-oil, reaction products with acrylic acid, potassium salt

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April -September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids tall-oil, reaction products with acrylic acid, potassium salt

Molecular formula:

not applicable to UVCB substances

IUPAC Name:

Fatty acids tall-oil, reaction products with acrylic acid, potassium salt

Test material form:

solid: bulk

Details on test material:

- Name of test material (as cited in study report): Diacid 1550, K-salt (trade name: "H-240 100%")
- Physical state: amber solid
- Storage condition of test material: At room temperature in original, sealed container

Specific details on test material used for the study:

Identification: H-240 100% a.s.
Synonyms: Diacid H-240; OCD 9142-055
CAS Number: 68127-33-3
Purity: 100%
Physical state/Appearance: amber colored solid
Expiry Date: 10 April 2018
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Wistar (RccHanTm:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 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 a cage card. At the start of the study the animals weighed at least 200 g, and were 8 to 12 weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The initial two animals were housed individually throughout the study. The further group of eight animals (four male and four female) were housed individually during the 24-hour exposure period and in groups of four, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
The diet, drinking water and bedding were routinely analyzed 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 relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70%, respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: For the purpose of the study the test item was weighed out according to each animal's individual body weight and moistened with distilled water prior to application.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males (2000 mg/kg), 5 females (2000 mg/kg)

Control animals:

no

Details on study design:

On the day before treatment the back and flanks of each animal were clipped free of hair.
In the absence of data suggesting the test item was toxic, one male and one female rat were initially treated with the test item at a dose level of 2000 mg/kg.
The appropriate amount of test item, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually throughout the study. 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 any residual test item.
As no mortalities were noted a further group of animals (four males and four females) was similarly treated with the test item at a dose level of 2000 mg/kg body weight to give a total of five males and five females. The animals were caged individually for the 24-hour exposure period. After the 24-hour contact period the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item. These animals were returned to group housing for the remainder of the test period.
The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS

Erythema and Eschar Formation
Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.
Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At 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 thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

The following computerized system was used in the study:
Delta Controls — ORCAview

Results and discussion

Preliminary study:

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. As no mortalities were noted a further group of animals (four males and four females) was similarly treated with the test item at a dose level of 2000 mg/kg body weight to give a total of five males and five females.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

No signs of systemic toxicity were noted during the observation period

Body weight:

One female showed no gain in body weight during the first week with expected gain in body weight during the second week and one other female showed expected gain in body weight during the first week but body weight loss during the second week. The remaining animals showed expected gains in body weight over the study period.

Gross pathology:

No abnormalities were noted at necropsy

Other findings:

Dermal reactions: Very slight or well-defined erythema and very slight or slight edema were noted at the test sites of all animals. Hemorrhage of dermal capillaries and/or small superficial scattered scabs were noted at the test sites of three animals. Scab cracking was also noted at the test site of one male. Loss of skin elasticity and flexibility was noted at the test sites of two males.

Any other information on results incl. tables

Individual clinical observations and mortality data

Dose Level mg/lig	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		Y2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Female	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 Dermal Reactions - Males

Dose Level mg/kg	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	Erythema	2	1	1	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Male	Erythema	2	2	2	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	2	2	0	0	0	0	0	0	0	0	0	0	0
		Other	0	Hd	Ss	Ss	0	0	0	0	0	0	0	0	0	0
	3-1 Male	Erythema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	LeLf	0	0	0	0	0	0	0	0	0	0	0
	3-2 Male	Erythema	2	2	2	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	2	2	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	Ss	SsSk	Ss	Ss	Ss	Ss	Ss	0	0	0	0	0
	3-3 Male	Erythema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	LeLf	0	0	0	0	0	0	0	0	0	0	0

0 = No reactions

Hd = Hemorrhage of dermal capillaries

Ss = Small superficial scattered scabs         

0 = Due to a technician error observation not recorded

Individual Dermal Reactions - Females

Dose Level mg/kg	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	Erythema	1	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	1	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Female	Erythema	2	2	1	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	2	1	0	0	0	0	0	0	0	0	0	0	0
		Other	0	Hd	Ss	Ss	Ss	Ss	Ss	Ss	Ss	0	0	0	0	0
	4-1 Female	Erythema	2	1	1	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Female	Erythema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Female	Erythema	2	2	1	0	0	0	0	0	0	0	0	0	0	0
		Edema	2	1	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No reactions

Hd = Hemorrhage of dermal capillaries

Ss = Small superficial scattered scabs         

0 = Due to a technician error observation not recorded

Individual Body Weights and Body Weight Changes

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Change (g) During Week
		0	7	14	1	2
2000	1-0 Male	260	282	319	22	37
	3-0 Male	287	306	326	19	20
	3-1 Male	281	303	320	22	17
	3-2 Male	284	305	328	21	23
	3-3 Male	269	284	302	15	18
	2-0 Female	222	250	245	28	—5
	4-0 Female	234	235	247	1	12
	4-1 Female	228	228	238	0	10
	4-2 Female	230	241	257	11	16
	4-3 Female	225	230	241	5	11

Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Male	Killed Day 14	No abnormalities detected
	3-0 Male	Killed Day 14	No abnormalities detected
	3-1 Male	Killed Day 14	No abnormalities detected
	3-2 Male	Killed Day 14	No abnormalities detected
	3-3 Male	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	4-0 Female	Killed Day 14	No abnormalities detected
	4-1 Female	Killed Day 14	No abnormalities detected
	4-2 Female	Killed Day 14	No abnormalities detected
	4-3 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

Methods

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. Based on the results of the initial test, a further group of eight animals (four males and four females) was equally treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Signs of dermal irritation noted were very slight to well-defined erythema, very slight to slight edema, hemorrhage of dermal capillaries, loss of skin elasticity and flexibility, small superficial scattered scabs and scab cracking.

Body Weight. One female showed no gain in body weight during the first week with expected gain in body weight during the second week and one other female showed expected gain in body weight during the first week but body weight loss during the second week. The remaining animals showed expected gains in body weight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

The acute dermal median lethal dose (LD₅₀) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight. Dermal irritation was low and below threshold for classification. Furthermore, all dermal irritation scores reduced over time, showing the effects being fully reversible.