12-hydroxy-N-(2-hydroxyethyl)octadecan-1-amide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg) or to establish a non-lethal dose level of 2000 milligram of test item per kilogram of body weight.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 12-hydroxyoctadecanoate

EC Number:

205-471-8

EC Name:

Methyl 12-hydroxyoctadecanoate

Cas Number:

141-23-1

Molecular formula:

C19H38O3

IUPAC Name:

Methyl 12-hydroxyoctadecanoate

Test material form:

solid: particulate/powder

Details on test material:

- Name of the test material: Methyl 12-hydroxyoctadecanoate
- IUPAC name: Methyl 12-hydroxyoctadecanoate
- Molecular formula: C19H38O3
- Molecular weight: 314.5062 g/mol
- Smiles: C(CCCCCCCCCCC(=O)OC)(CCCCCC)O
- Inchi: 1S/C19H38O3/c1-3-4-5-12-15-18(20)16-13-10-8-6-7-9-11-14-17-19(21)22-2/h18,20H,3-17H2,1-2H3
- Substance type: Organic
- Physical state: White powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult female rats aged between 8 – 10 weeks were used.
- Weight at study initiation: The weight ranges of approximately 219.1 to 232.4 grams at initiation of dosing were used.
Body weights at the start :
Female
Mean : 225.52 g (= 100 %)
Minimum : 219.1 g (- 2.85 %)
Maximum : 232.4 g (+ 3.05 %)
Total No. of animals : 5
- Fasting period before study: No data
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3 to 21.8 degree centigrade.
- Humidity (%):55.4% to 59.2%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 17-02-2018 to 12-03-2018

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

(Distilled water)

Details on dermal exposure:

TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No data
- For solids, paste formed: Yes

Duration of exposure:

24 hours

Doses:

A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).

No. of animals per sex per dose:

2000 mg/kg bw:2 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction:
Dermal reaction was observed daily for study period of 14 days.

Body weights:
Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:

No data

Results and discussion

Preliminary study:

Dose Range Finding Study: A single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered at the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.
Main Study: Group II : Animals treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.

Clinical signs:

other: Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Group I : Animal treated at the dose level of 1000 mg/kg body weight did

Gross pathology:

Gross pathological examination did not reveal any abnormalities in animals from 200 mg/kg, 1000 mg/kg and 2000 mg/kg dose groups from dose range finding study and main study sacrificed terminally.

Other findings:

- Other observations: Evaluation of Dermal Reaction
Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Main Study: Group II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Any other information on results incl. tables

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	200	No clinical signs observed	1	1	Day 0 - Day 14	0/1

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	1000	No clinical signs observed	1	2	Day 0 - Day 14	0/1

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	1	3	Day 0 - Day 14	0/1

 

Main Study:

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
II	2000	No clinical signs observed	2	4, 5	Day 0 - Day 14	0/2

 

 

Table No. II 

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Female 

Dose Finding Study:

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to
I	200	No dermal reaction observed	1	1	Day 0 - Day 14

 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to
I	1000	No dermal reaction observed	1	2	Day 0 - Day 14

 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to
I	2000	No dermal reaction observed	1	3	Day 0 - Day 14

 

Main Study:

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to
II	2000	No dermal reaction observed	2	4, 5	Day 0 - Day 14

 

Table No.III

 

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Female

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	200	Mean	219.4	226.6	3.28	235.3	3.84	7.25
		± SD	-	-	-	-	-	-

 

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	1000	Mean	219.1	225.6	2.97	231.7	2.70	5.75
		± SD	-	-	-	-	-	-

 

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	232.4	240.0	3.27	245.2	2.17	5.51
		± SD	-	-	-	-	-	-

 

Main Study:

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	2000	Mean	228.35	233.90	2.43	243.60	4.14	6.67
		± SD	4.60	4.67	0.02	6.22	0.58	0.58

 

Table No.IV

 

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Female

 Dose Finding Study:

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	200	1	TS	No abnormality detected

 

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	1000	2	TS	No abnormality detected

 

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	3	TS	No abnormality detected

 

Main Study:

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	2000	4, 5	TS	No abnormality detected

 

TS = Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal LD50 value was considered to be >2000 mg/kg body weight, when female Sprague Dawley rats were treated with the given test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Executive summary:

The acute dermal toxicity study was conducted according to OECD Guideline 402 (Acute Dermal Toxicity) in female Sprague Dawley rats. In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours. As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals. Animals from dose range finding study treated at the dose levels of 200 mg/kg, 1000 mg/kg and 2000 mg/kg and animals from main study treated at the dose level of 2000 mg/kg exhibited normal body weight gain and revealed no clinical signs of toxicity or mortality during the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Thus, the acute dermal LD50 value was considered to be >2000 mg/kg body weight, when female Sprague Dawley rats were treated with the given test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).