N,N'-dithiodi-o-phenylenedibenzamide

Endpoint summary

Description of key information

Not found to be hazardous by ingestion or in contact with skin

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Testing carried out in accordance to: OECD Guideline for testing of Chemicals (No. 401. Acute Oral Toxicity, Feb, 1987) State Environmental Protection Administration: The Guidelines for the Testing of Chemicals Ministry of Health, 2005: Technical Standards for testing of chemicals

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: State environmental protection administration: the guidelines for the testing of chemicals

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Ministry of health 2005: Technical standards for testing of chemicals

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: NIH

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test species: Mice.
Strain: NIH.
Supplier: Guangdong Medical Laboratory Animal Center [certified animal number SCXK (Guangdong) 2008-0002].
Number of animals: 10 males and 10 females.
Number of groups: 2(test group and solvent control group).
Number of animal/group: 5 males and 5 females per group.
Body weight at the start of experiment: 22.4 ～ 32.3g .
Identification of animals: Tags marked with animal group number and treatment details were attached to cages. Each animal was given a unique number.
Acclimatization: Five days prior to the experiment in the test room.
Randomization: Animals were assigned to two groups.

Environmental conditions
Test Room: SPF animal lab in the Center
Animal house conditions: The test facility was an air-conditioned room with 12h artificial fluorescent light and 12h dark.
Temperature range: 20~25oC.
Humidity range: 40~70%.

Husbandry Practices
Caging: Stainless steel cages were used. Autoclaved clean dry corncob was used as the bedding material. Animals were housed in one group according to sex in cages.
Water bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Sanitation: Bedding material was changed daily.
Food and water: Standard pellet feed supplied by Guangdong Medical Laboratory Animal Center and ultra-pure filtered sterilized water were provided to the animals freely.
Frequency of providing feed and drinking water: Both drinking water and feed were provided ad libitum.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Preparation of test substance: Known weights of the test substance were mixed with distilled water, and thereafter administered to groups of mice at the desired dose levels.

Doses:

Administration: All mice were fasted overnight prior to administration on of the test substance. The tested animals (5 males and 5 females each group) were given Pepton 22 ,which was dissolved in distilled water, by gavages at the dose of 5050 mg/kg and at the volume of 10ml/kg for once; Animals of solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group.

Dose levels: A limit test at one dose level of 5050 mg/kg was carried out with mice (5 males and 5 females); the solvent control group was given distilled water instead of tested compounds was carried out with mice (5 males and 5 females) too.

No. of animals per sex per dose:

Number of animals: 5 males and 5 females per group.

Control animals:

yes

Details on study design:

Acute oral toxicity of Pepton 22 was tested in two groups of mice. The tested animals (5 males and 5 females each group) were given Pepton 22 ,which was dissolved in distilled water, by gavages at the dose of 5050 mg/kg and at the volume of 10ml/kg for once; Animals of solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group. Mice were observed for 14 days after the exposure. At the end of the test, all survivals were weighed and sacrificed, and necropsy were carried out. Body weight of the animals were recorded before and weekly after exposure.

Observation period: All animals were observed individually, daily for 14 days for various end-points of toxicity.

Body weight: Body weight of each animal was recorded just prior to administration of dose (0 day) and on day 7 and day 14 following the dosing.

Mortality: All animals were observed for mortality daily throughout the observation period.

Toxicity: All animals were observed for toxicity signs soon after dosing and once daily throughout the observation period until day 14 when the experiment was terminated.

Necropsy: Survivors were necropsied at the end of 14-day observation period for gross pathological examination. Autopsy was carried out in animals died during the observation period.

Preliminary study:

Acute oral LD50 of Pepton 22 (supplied by Thomas Swan ＆ Co. Ltd.) was greater than 5050 mg/kg both in female and male NIH mice.
Based on Globally Harmonized System of classification and Labelling of Chemicals (GHS), Pepton 22 was classified as category 5. Referring to “Acute oral, inhalation, dermal toxicity grading” of “The guidelines for the hazard evaluation of new chemical substance” (HJ/T 154-2004), State Environmental Protection Administration, Pepton 22 was “Actually Nontoxic”.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 050 mg/kg bw

Mortality:

Result of the acute oral toxicity test on Pepton 22, no mortality was observed in the treated group of mice throughout the observation period (Table 1).

Clinical signs:

other: In the dose level of 5050 mg/kg, all the animals were no abnormalities detected except slight inactivity. There was no mortality observed in mice treated with the test substance throughout the observation period.

Gross pathology:

No gross abnormalities were seen in the group of animals at necropsy at the end of 14-day observation period (Table 4).

Mortality Data and LD₅₀

Table 1

Groups		Female			Male
		Animal number of each group	Dead animals		Animal number of each group	Dead animals
5050mg/kg		5	0		5	0
solvent control		5	0		5	0
LD50(95％CI)		＞5050mg/kg(not elicited)			＞5050mg/kg(not elicited )

 

Body weight

Table 2

Groups	Gender	No.	0d		7d	14d
			weights		weights	weights
5050 mg/kg	♀	1	23.9		23.9	28.3
		4	26.0		27.0	34.1
		5	26.4		26.4	32.5
		6	24.6		26.0	33.0
		8	25.9		28.7	35.2
	♂	1	28.8		32.8	40.4
		4	30.0		37.5	43.6
		7	30.1		34.1	41.7
		9	32.7		37.4	44.0
		10	29.2		34.6	39.7
solvent control	♀	2	26.2		27.4	32.3
		3	25.3		28.4	34.0
		7	26.1		27.4	33.5
		9	22.4		23.7	29.7
		10	25.9		29.2	34.5
	♂	2	31.0		40.3	45.1
		3	29.3		36.1	42.0
		5	29.2		34.0	39.8
		6	28.0		32.6	39.1
		8	32.3		39.2	46.3

 

 

Table 3

Groups	Gender	0d	7d	14d
5050mg/kg	Female	25.4±1.1（5）	26.4±1.7（5）	32.6±2.6（5）
	Male	30.2±1.5（5）	35.3±2.1（5）	41.9±1.9（5）
solvent control	Female	25.2±1.6（5）	27.2±2.1（5）	32.8±1.9（5）
	Male	30.0±1.7（5）	36.4±3.3（5）	42.5±3.2（5）

 

Gross pathology data

Table 4

Groups	Gender	No.	Lesions	Groups	Gender	No.	Lesions
5050mg/kg	♀	1	NAD	solvent control	♀	2	NAD
		4	NAD			3	NAD
		5	NAD			7	NAD
		6	NAD			9	NAD
		8	NAD			10	NAD
	♂	1	NAD		♂	2	NAD
		4	NAD			3	NAD
		7	NAD			5	NAD
		9	NAD			6	NAD
		10	NAD			8	NAD

 

NAD – no abnormalities detected

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Data shows that material is not classified according to REGULATION (EC) No 1272/2008

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 050 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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: see 'Remark'

Remarks:

Testing carried out in accordance to: OECD Guideline for Testing of Chemicals No. 402. Acute Dermal Toxicity, Feb. 1987 State Environmental Protection Administration : The Guidelines for the Testing of Chemicals Ministry of Health, 2005: Technical standards for testing of chemicals .

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: State Environmental Protection Administration : The Guidelines for the Testing of Chemicals

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Ministry of Health, 2005: Technical standards for testing of chemicals

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test species: Rats.
Strain: SD.
Supplier: Guangdong Medical Laboratory Animal Center [certified animal number SCXK (Guangdong) 2008-0002].
Number of animals: 10 males and 10 females.
Number of groups: 2(test group and solvent control group).
Number of animal/group: 5 males and 5 females per group.
Body weight at the start of experiment: 197 ～ 274g .
Identification of animals: Tags marked with animal group number and treatment details were attached to cages. Each animal was given a unique number.
Acclimatization: Five days prior to the experiment in the test room.
Randomization: Animals were assigned to two groups.

Environmental conditions
Test Room: SPF animal lab in the Center
Animal house conditions: The test facility was an air-conditioned room with 12h artificial fluorescent light and 12h dark.
Temperature range: 20~25oC.
Humidity range: 40~70%.

Husbandry Practices
Caging: Stainless steel cages were used. Autoclaved clean dry corncob was used as the bedding material. Animals were housed in one group according to sex in cages.
Water bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Sanitation: Bedding material was changed daily.
Food and water: Standard pellet feed supplied by Guangdong Medical Laboratory Animal Center and ultra-pure filtered sterilized water were provided to the animals freely.
Frequency of providing feed and drinking water: Both drinking water and feed were provided ad libitum.

Type of coverage:

open

Vehicle:

water

Details on dermal exposure:

Test Procedure: An area of about 5×8 cm2 on the back of the animal was clipped free of hair. 24h later, the intact animals were selected to use. Pepton 22 was administered on the hair-free site of the rats. The rats were fasten in the stainless steel shelves for 24h, then the test site were cleaned with warm water. Animals of the test group were conducted in the 2500 mg/kg dose limit test, the solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group.

Control animals:

yes

Details on study design:

Acute dermal toxicity of Pepton 22 (supplied by Thomas Swan ＆ Co. Ltd.) was tested in two groups of Rats. Pepton 22 was administered on the hair-free site of the rats. The rats were fasten in the stainless steel shelves for 24h, then the test site were cleaned with warm water. Animals of the test group were conducted in the 2500 mg/kg dose limit test, the solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group. Rats were observed for 14 days after the exposure. At the end of the test, all survivals were weighed and sacrificed, and necropsy were carried out. Body weight of the animals was recorded before and weekly after exposure.

Preliminary study:

Acute dermal LD50 of Pepton 22 (supplied by Thomas Swan ＆ Co. Ltd.) was greater than 2500 mg/kg both in female and male SD rats.
Based on Based on Globally Harmonized System of classification and Labelling of Chemicals (GHS), Pepton 22 was classified as category 5. According to “Acute oral、inhalation、dermal toxicity grading” of “The guidelines for the hazard evaluation of new chemical substance” (HJ/T 154-2004), State Environmental Protection Administration, Pepton 22 was “Actually Nontoxic”.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Mortality:

Result of the acute dermal toxicity test on Pepton 22, no mortality was observed in treated group of rats throughout the observation period (Table 1).

Clinical signs:

other: In the dose level of 2500 mg/kg, all the animals were no abnormalities detected except slight inactivity. There was no mortality observed in rats treated with the test substance throughout the observation period.

Gross pathology:

No gross abnormalities were seen in the group of animals at necropsy at the end of 14-day observation period (Table 4).

Mortality Data and LD₅₀

Table 1

Groups		Female					Male
		Animal number of each group		Dead animals			Animal number of each group	Dead animals
2500mg/kg			5		0		5	0
solvent control			5		0		5	0
LD50(95%CI)			>2500mg/kg(not elicited)				>2500mg/kg(not elicited )

 

Body weight

Table 2

Groups	Gender	No.	0d	7d	14d
			weights	weights	weights
2500 mg/kg	♀	1	203	235	254
		3	197	218	238
		7	214	234	262
		8	211	229	254
		12	204	231	250
	♂	2	257	292	337
		3	270	309	347
		4	267	300	347
		7	257	306	344
		12	241	284	330
solvent control	♀	2	201	221	239
		4	207	233	258
		5	207	231	265
		9	202	202	246
		10	224	245	273
	♂	1	265	313	346
		5	274	318	368
		8	262	315	359
		9	252	306	362
		10	255	297	353

 

 

 

 

 

 

Table 3

Groups	Gender	0d	7d	14d
2500mg/kg	Female	205.8±6.8 (5)	229.4±6.8 (5)	251.6±8.8  (5)
	Male	258.4±11.3 (5)	298.2±10.2 (5)	341.0±7.4 (5)
solvent control	Female	208.2±9.2 (5)	226.4±16.1 (5)	256.2±13.8 (5)
	Male	261.6±8.7 (5)	309.8±8.4 (5)	357.6±8.4 (5)

 

Gross pathology data

Table 4

Groups	Gender	No.	Lesions	Groups	Gender	No.	Lesions
2500 mg/kg	♀	1	NAD	solvent control	♀	2	NAD
		4	NAD			3	NAD
		5	NAD			7	NAD
		6	NAD			9	NAD
		8	NAD			10	NAD
	♂	1	NAD		♂	2	NAD
		4	NAD			3	NAD
		7	NAD			5	NAD
		9	NAD			6	NAD
		10	NAD			8	NAD

 

NAD – no abnormalities detected

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Data shows that material is not classified according to REGULATION (EC) No 1272/2008

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Additional information

Acute toxicity: oral mouse = >5050 mg/kg Dermal Rat = >2500 mg/kg Inhalation not performed as exposure unlikely