3-acetylthiazolidine-4-carboxylic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

3-acetylthiazolidine-4-carboxylic acid

EC Number:

225-713-6

EC Name:

3-acetylthiazolidine-4-carboxylic acid

Cas Number:

5025-82-1

Molecular formula:

C6H9NO3S

IUPAC Name:

3-acetylthiazolidine-4-carboxylic acid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Doses:

Dose-range Finding Study
The purpose of the dose-range finding study is selection of the appropriate starting dose for the main study. The starting dose could be selected from the fixed dose levels of 50, 200, 1000, and 2000 mg/kg body weight.
The test item information was available, a limit dose of 2000 mg/kg body weight was used as starting dose. One female was dosed. The test item-related mortality was not observed during 48 hours. The dose-range finding study was finished; the main test was started with dose of 2000 mg/kg body weight.
Main Study
Based on the outcome in the dose-range finding study, the main study was conducted with 2 further animals to confirm the classification outcome. The additional 2 females were dosed with the dose of 2000 mg/kg body weight. A total of three female rats were dosed with a limit dose of 2000 mg/kg body weight.

No. of animals per sex per dose:

3 females, animals were non-pregnant and nulliparous.

Details on study design:

Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving.
The required amount of the test item (according to the body weight and dose) moistened with the vehicle (0.5 mL) was applied directly on the shaved skin of the back uniformly on an area approximately 10 % of a total body surface area. The test item was held in contact with the skin by using semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water.

Results and discussion

Preliminary study:

All, 3/3 females survived the limit dose of 2000 mg/kg body weight. Summary results of clinical observation are presented in Table 2. On day 3 and 4 (48 and 72 hours after dressing removing), the very slight redness of skin at the application site was found in the animal No. 2 treated with a 2000 mg/kg body weight dose as pale pink spot assigned as erythema of score 1.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Body weight:

other body weight observations

Remarks:

Mildly increase of the body weight of animals was observed.

Any other information on results incl. tables

      RESULTS

1      Clinical Observation

All, 3/3 females survived the limit dose of 2000 mg/kg body weight. Summary results of clinical observation are presented in Table 2. On day 3 and 4 (48 and 72 hours after dressing removing), the very slight redness of skin at the application site was found in the animal No. 2 treated with a 2000 mg/kg body weight dose as pale pink spot assigned as erythema of score 1. Observation results of the treatment skin 24, 48 and 72 hours after removal of the test item are presented in Table 3.

 

 

Table 2 Clinical Observation

Sex	Dose	ID	Administration  Result	Clinical Observation
♀	2000 mg/kg	1	alive	no signs of intoxication, change of health, nor any adverse reactions during 14-days observation period
		2	alive	no signs of intoxication, change of health, nor any adverse reactions during 14-days observation period
		3	alive	no signs of intoxication, change of health, nor any adverse reactions during 14-days observation period

                                                                                                                

Table 3 Skin Reaction Score

Sex	Dose	ID	24 hours		48 hours		72 hours
			Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
♀	2000 mg/kg	1	0	0	0	0	0	0
		2	0	0	1	0	1	0
		3	0	0	0	0	0	0

ID 2 – 96 hours after dressing removing without erythema

2       Body Weight

Mildly increase of the body weight of animals was observed. Summary results of body weight development are presented in Table 4.

Table 4 Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	201	201	209	0	8	8
		2	191	200	217	9	26	17
		3	186	194	205	8	19	11

3       Necropsy

All animals were necropsied. During necropsy, no macroscopic changes were noticed. Necropsy results are presented in Table 5.

Table 5 Necropsy Results

Sex	Dose	ID	Result
♀	2000 mg/kg	1	no finding
		2	no finding
		3	no finding

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of the test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine is greater than 2000 mg/kg body weight after single dermal application to Wistar rats.
Based on OECD Test Guideline 402 Acute Dermal Toxicity: Fixed Dose Procedure it can be concluded that the test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine according to the Globally Harmonised System can be classified in Category 5/Unclassified after single dermal application to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine when applied as a single dermal dose to Wistar rats. The procedure according to OECD Test Guideline 402 Acute Dermal Toxicity: Fixed Dose Procedure was used.
Test item information were available, a limit dose of 2000 mg/kg body weight was used as starting dose. One female was dosed. Test item-related mortality was not observed during 48 hours. Based on the outcome in the dose-range finding study, the main study was conducted with 2 further animals to confirm the classification outcome. A total of three female rats were dosed with a limit dose of 2000 mg/kg body weight.
The test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine applied to 3 females at a limit dose of 2000 mg/kg body weight did not cause death. Mildly increase of the body weight of animals was observed. No signs of intoxication, change of health, nor any other adverse reactions during 14-days observation period was observed. The test item did cause very slight erythema on the skin of one test animal. Erythema disappeared within 96 hours after dressing removing. During necropsy, no macroscopic findings were observed.
The LD50 of the test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine is greater than 2000 mg/kg body weight after single dermal application to Wistar rats.
Based on OECD Test Guideline 402 Acute Dermal Toxicity: Fixed Dose Procedure it can be concluded that the test item 3-Acetylthiazolidine-4-carboxilyc acid, synonym Folcisteine according to the Globally Harmonised System can be classified in Category 5/Unclassified after single dermal application to Wistar rats.