N-hydroxysuccinimide

Carcinogenicity

Description of key information

Supporting study: Painting test. The test item seemed to be non-carcinogenic after dermal application in mice, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Supporting study: Injection test. The test item seemed to be non-carcinogenic after subcutaneous injection in rats up to 420 mg/animal, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1971

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

no guideline available

Principles of method if other than guideline:

- Method: Mouse Skin-painting test
- Principle of test: To determine potential carcinogenicity of a chemical.
- Short description of test conditions: Repeated applicatoin of a chemical to the sahved skin on the back throughout all or most of the lifespan of the mouse.
- Parameters analysed / observed: Clinical observation of papillomas and carcinomas in the treated area.

GLP compliance:

no

Species:

mouse

Strain:

other: SaB

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: 3 months

Route of administration:

dermal

Vehicle:

acetone

Details on exposure:

TEST SITE
- Area of exposure: Shaved neck skin
- Time intervals for shavings or clipplings: one week before the star of the experiment

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 drops
- Concentration (if solution): 0.4%
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): 2 drops

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

18 months

Frequency of treatment:

Twice weekly

Post exposure period:

The animals were observed up to 18 months after treatment initiation

Dose / conc.:

0.4 other: %

Remarks:

2 drops of a 0.4% solution

No. of animals per sex per dose:

7 male and 8 female rats

Control animals:

yes, concurrent vehicle

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): No data

BODY WEIGHT: No data

OTHER: Mortality and tumor formation were observed.

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No mortality related to treament was observed during the test.

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Description (incidence and severity):

No tumors were formed due to treament during the test.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

No tumors were observed during the experiment.

 

Table 1. Carcinogenesis effects of n-hydroxysuccinimide (NHS) after dermal administration in mice.

	Nº of animals after
	0 Months	6 Months	12 Months	18 Months*	Tumors
NHS	15	15	13	5	No
Control	15	15	10	1	No

NHS: N-hydroxysuccinimide

*After experiment initiation

 

Conclusions:

The test item seemed to be non-carcinogenic after dermal application in mice, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Executive summary:

A skin-painting study of the test item was performed in SaB mice. Fifteen mice, 7 male, and 8 female, were shaved in the neck one week before the start of the experiment. The animals were given twice weekly two drops of a 0.4% solution of test item in acetone up to their natural death. A control group was given acetone in parallel. The animals were observed for 18 months after the experiment initiation. None of the animals showed any tumors during the whole experiment. Under these experimental conditions, the test item seems to be non-carcinogenic, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Reference 2

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1971

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

no guideline available

Principles of method if other than guideline:

- Method: Subcutaneous injection test
- Principle of test: To determine potential carcinogenicity of a chemical.
- Short description of test conditions: Administration of a single or repeated dose of a chemical injected subcutaneously into rats.
- Parameters analysed / observed: The development of tumors in the injection site or another part of the body.

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: 3-4 months

Route of administration:

subcutaneous

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

21 weeks

Frequency of treatment:

Once weekly

Post exposure period:

The animals were observed up to 24 months after treatment initiation

Dose / conc.:

420 other: mg / animal

No. of animals per sex per dose:

7 male and 8 female rats

Control animals:

no

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

DERMAL IRRITATION (if dermal study): No data

BODY WEIGHT: No data

OTHER: Mortality and tumor formation were observed.

Clinical signs:

not specified

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Description (incidence):

No mortality related to treatment was observed during the test.

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Description (incidence and severity):

No tumors were formed due to treatment during the test.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOEL

Effect level:

420 other: mg / animal

Based on:

test mat.

Sex:

male/female

Basis for effect level:

gross pathology

mortality

No tumors were observed during the experiment.

Table 1. Carcinogenesis effects of n-hydroxysuccinimide (NHS) after subcutaneous injection in rats

NHS	Nº of animals after
	0 Months	6 Months	12 Months	18 Months	24 Months*	Tumors
420 mg	15	15	15	13	9	None

*After experiment initiation

 

Conclusions:

The test item seemed to be non-carcinogenic after subcutaneous injection in rats up to 420 mg/animal, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Executive summary:

In order to determine the carcinogenic potential of the test item, an injection test was performed in Sprague-Dawley rats. Fifteen rats, 7 male, and 8 female, were given once weekly subcutaneously 2 ml of a physiological saline solution containing 420 mg of test item for a period of 21 weeks. The animals were observed for up to 24 months after the experiment initiation. None of the animals showed any tumors during the whole experiment. Under these experimental conditions, the test item seems to be non-carcinogenic up to 420 mg/animal, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

Klimish score 3.

Justification for classification or non-classification

Due to the insufficient data, the test item cannot be classified as carcinogenic according to CLP Regulation (EC) no. 1272/2008.

Additional information

Supporting study: A skin-painting study of the test item was performed in SaB mice. Fifteen mice, 7 male, and 8 female, were shaved in the neck one week before the start of the experiment. The animals were given twice weekly two drops of a 0.4% solution of test item in acetone up to their natural death. A control group was given acetone in parallel. The animals were observed for 18 months after the experiment initiation. None of the animals showed any tumors during the whole experiment. Under these experimental conditions, the test item seems to be non-carcinogenic, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.

Supporting study: In order to determine the carcinogenic potential of the test item, an injection test was performed in Sprague-Dawley rats. Fifteen rats, 7 male, and 8 female, were given once weekly subcutaneously 2 ml of a physiological saline solution containing 420 mg of test item for a period of 21 weeks. The animals were observed for up to 24 months after the experiment initiation. None of the animals showed any tumors during the whole experiment. Under these experimental conditions, the test item seems to be non-carcinogenic up to 420 mg/animal, based on the number of tumors. However, no conclusion can be drawn due to the insufficient data.