cyclic C12/14-Glucamide;cyclic N-methyl-N-dodecanoyl/tetradecanoyl-glucamine;anhydro-N-dodecanoyl/tetradecanoyl-N-methylglucamine;Amides, C12-C14, N-(1-deoxy-D-glucitol-1-yl)-N-methyl, dehydrated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 February 2022 to 11 March 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 402 (Section 4: Health Effects) “Acute Dermal Toxicity: Fixed Dose Procedure” adopted on 09 October 2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

D-Glucitol, anhydro-1-deoxy-1-(methylamino)-, N-[C12-14(even numbered) acyl] derivs.

Molecular formula:

C19H37NO5 C21H41NO5

IUPAC Name:

D-Glucitol, anhydro-1-deoxy-1-(methylamino)-, N-[C12-14(even numbered) acyl] derivs.

Test material form:

semi-solid (amorphous): gel

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Clariant and S148866
- Expiration date of the batch: 30.09.2022

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No
- Final preparation of a solid: applied as such

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 200.45 g to 201.69 g
- Fasting period before study: No
- Housing: polysulphonate cage (size: L 430 x B 280 x H 210 mm)
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: 18 Feb 2022 to 24 Feb 2022

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0°C to 22.8°C
- Humidity (%): 44% to 66%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 18 Feb 2022 To: 11 Mar 2022

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 6 cm × 10 cm
- % coverage: 10% of the total body surface
- Type of wrap if used: crepe bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 Hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 420.3 mg for range-finding study; 439.3 and 440.3 mg for main study
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Range-finding study: 1 animal
Main study: 2 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation once daily and weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical sign and body weight

Statistics:

No

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality

Clinical signs:

other: No treatment related clinical signs of toxicity and mortality were observed in both range finding study and main study animals

Gross pathology:

No treatment related gross pathological changes were observed in any of the animals in both range finding study and main study

Any other information on results incl. tables

 

TABLE 1.     INDIVIDUAL ANIMAL CLINICAL SIGNS OF TOXICITY ANDMORTALITY RECORD

Phase of the Experiment

Dose (mg/kg body weight)

Animal No.

Sex

Time of Application

Clinical Signs of Toxicity and Mortality on Day 1

Clinical Signs of Toxicity and Mortality on days

20-30 mins

1 hr (±10 mins)

2 hrs (±10 mins)

4 hrs (±10 mins)

6 hrs (±10 mins)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Range Finding Study

2000

Rg6745

F

11:44

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Main Study

2000

Rg6746

F

11:45

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rg6747

F

11:46

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

    N: Normal; F: Female; mins: minutes; hr/hrs: hour/hours

 

 TABLE 2.  INDIVIDUAL ANIMAL SKIN REACTION SCORE RECORDD

Phase of the Experiment	Dose (mg/kg body weight)	Sex	Animal No.	Skin Reaction Observations	Skin Reaction Score on Days
					3                (24 hour)	4                  (48 hour)	5             (72 hour)
Range Finding Study	2000	F	Rg6745	ER	0	0	0
				ED	0	0	0
Main Study	2000	F	Rg6746	ER	0	0	0
				ED	0	0	0
		F	Rg6747	ER	0	0	0
				ED	0	0	0

      F: Female; ER: Erythema; ED: Edema; 0: No erythema and no edem

 

 

 

TABLE 3.INDIVIDUAL ANIMAL BODY WEIGHT (g) AND PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1

Phase of the Experiment	Dose (mg/kg body weight)	Animal No.	Sex	Quantity of test item applied (mg)	Body Weight (g) on Days				Percent Change in Body Weight with Respect to Day
					1	8	15		1 to 8	1 to 15
Range Finding Study	2000	Rg6745	F	420.3	210.15	228.61	245.13		8.78	16.65
Main Study	2000	Rg6746	F	439.3	219.65	236.13	252.73		7.50	15.06
		Rg6747	F	440.3	220.16	238.21	256.41		8.20	16.47
				Mean	219.91	237.17	254.57		7.85	15.76
				±SD	0.36	1.47	2.60		0.49	0.99
				n	2	2	2		2	2

     F: Female; SD: Standard Deviation; n: Number of animals

 

 

Quantity of Test Item Applied (mg)	=	Dose / 1000 X Body weight (g)
	=	2000 / 1000 X 210.15
	=	420.3 mg

 

 

 

 

TABLE 4.    INDIVIDUAL ANIMALGROSS PATHOLOGY FINDINGS

Phase of the Experiment	Dose (mg/kg body weight)	Animal No.	Sex	Fate	Gross Pathology Findings
					External	Internal
Range finding Study	2000	Rg6745	F	TS	NAD	NAD
Main Study	2000	Rg6746	F	TS	NAD	NAD
		Rg6747	F	TS	NAD	NAD

 NAD: No Abnormality Detected; F: Female;TS: Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions employed and based on the above results, it is concluded that the acute dermal median lethal dose (LD50) of test item, Cyclic Glucamide C12-C14 in Sprague Dawley rats is >2000 mg/kg body weight.

Executive summary:

 

The test item Cyclic Glucamide C12-C14 was evaluated for Acute Dermal Toxicity study in Sprague Dawley Rats.

The study was performed in two phases i.e. range finding study and main study. Range finding study was performed with one female rat and main study was performed with two female rats. On the day before the application of the test item, fur on the dorso-lateral area of the trunk of the animals was removed by clipping closely with an electric hair clipper and care was taken to avoid abrading the skin.

The required quantity of the test item was applied as uniform film over an area of approximately 10% of the total body surface. The test item was held on to the applied surface by covering with cotton gauze dressing and wrapped with non-irritating adhesive tape and finally the application site was wrapped using semi-occlusive crepe bandage. The contact period of test item was 24 hours. At the end of the contact period, the residual test item was washed using distilled water and dried with absorbent cotton.

The animals were dosed in a stepwise procedure with one female rat at a time in range finding study. Since the LD₅₀of structure analogues is >2000 mg/kg body weight based on information provided by sponsor and as per the material safety data sheet provided by sponsor the LD₅₀of test item is >2000 mg/kg body weight, a starting dose of 2000 mg/kg body weight was selected from the fixed dose levels of 50, 200, 1000 and 2000 mg/kg body weight. No clinical signs and mortalities were observed at the dose level of 2000 mg/kg body weight in range finding study. Hence, during main study, two animals were administered with the same dose level of 2000 mg/kg body weight. No clinical signs and mortalities were observed at the dose level of                 2000 mg/kg body weight. Hence, no further testing was carried out.

All the animals were observed for clinical signs of toxicity and mortality at               20 to 30 min, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs                  (±10 mins) post dosing on day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Skin reactions were scored at 24, 48 and 72 hours after patch removal using draize scoring system. The body weight was recorded at receipt, on day 1 before test item application and on days 8 and 15. At the end of observation period, all the animals were humanely sacrificed by carbon dioxide asphyxiation and subjected to necropsy and detailed gross pathological examination.

No mortality and clinical signs were noted.

No skin reactions were noted at 24, 48 and 72 hours after patch removal.

No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period. 

No treatment related gross pathological changes were noted at 2000 mg/kg body weight (range finding study and main study) during necropsy