N,N'-diacetylhydrazine

Endpoint summary

Description of key information

- Skin: not corrosive, Transcutaneous electrical resistance test (TER), similar to OECD 430, Pooles 2004c
- Eye: not irritating, enucleated rabbit eyes,  method described by Burton et al. (1981), Pooles 2004d
- Eye: not irritating, male, rabbit, OECD 405, Pooles 2004e
- Respiratory: no study available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

from 2004-02-26 to 2004-03-02 (experimental phase)

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is a screening study which did not formally follow a guideline method, and was not formally performed under audited GLP, however, the laboratory facilities were operated according to GLP. The purity of the test material was not reported and the documentation in the report was very limited. Although the results are considered valid, the screening study itself cannot be considered formally reliable due to the lack of formal guideline, quality assurance, and very limited documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))

Deviations:

no

GLP compliance:

no

Remarks:

This study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report has not been audited by the QA Unit. No formal claim of GLP compliance is made for this study.

Species:

rat

Strain:

Wistar

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported

Details on study design:

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

SCORING SYSTEM: The substance is considered likely to be corrosive in vivo if the mean electrical resistance is below 5kΩ.

Irritation parameter:

other: electrical resistance (kΩ)

Basis:

mean

Time point:

other: 24 hours

Score:

29.6

Remarks on result:

other: Standard deviation: 4.7 kΩ. Values below 5kΩ are considered to be corrosive.

Irritant / corrosive response data:

The measured mean electrical resistance was 29.6 ± 4.7 kΩ.

Interpretation of results:

other: not corrosive (skin corrosive category 1)

Conclusions:

Although the result is considered to be valid, due to the lack of formal guideline and quality assurance, and very limited documentation, it must be regarded as not being reliable.

Executive summary:

The skin corrosivity potential of the test material was assessed using the Transcutaneous Electrical Resistance Assay (TER). This involved the application of the test material to the epidermal surface of skin discs, obtained from a humanely killed young Wistar strain rat.

The prepared pelt from the rat was used for skin disc preparation. The test material was applied to the epidermal surface of three skin discs for a contact period of 24 hours. At the end of the contact period the test material was removed using a jet of warm tap water. Corrosive substances produce an irreversible loss of normal stratum corneum integrity and function, this is measured as a reduction in the inherent TER. A threshold value has been established (5 kΩ) below which materials are considered likely to be corrosive in vivo. The TER was measured using a low voltage alternating current electronic databridge.

The measured mean electrcal resistance was 29.6 ± 4.7 kΩ and thus, the test material was considered not to have the potential to be corrosive to the skin in vivo under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

from 2004-03-15 to 2004-03-25 (experimental phase)

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is a screening study which was not formally performed under audited GLP, however, the laboratory facilities were operated according to GLP. The purity of the test material was not reported and the documentation in the report was very limited. All raw data (observations) were reported. Although the results are considered valid, the screening study itself cannot be considered formally reliable due to the lack of quality assurance, and very limited documentation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Remarks:

This study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report has not been audited by the QA Unit. No formal claim of GLP compliance is made for this study.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No details on test animals and environmental conditions are reported.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (81 mg)

Duration of treatment / exposure:

single application

Observation period (in vivo):

Ocular reactions were recorded 1, 24,48 and 72 hours after administration.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: not reported

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0

Max. score:

110

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Individual Scores and Individual Total Scores for Ocular Irriation

Rabbit number and sex	38 Male				52 Male				157 Male
	Initial Pain Reaction = 3				Initial Pain Reaction = 0 *				Initial Pain Reaction = 0 *
Time after treatment [h]	1	24	48	72	1	24	48	72	1	24	48	72
Cornea
E=Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
F=Area of Cornea involved	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F x 5)	0	0	0	0	0	0	0	0	0	0	0	0
Iris
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae
A=Redness	1	0	0	0	1	1	0	0	1	1	0	0
B=Chemosis	0	0	0	0	0	0	0	0	0	0	0	0
C=Discharge	1	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	4	0	0	0	4	2	0	0	4	2	0	0
Total Score	4	0	0	0	4	2	0	0	4	2	0	0

* One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is not considered to be an eye irritant according to the criteria set out in Regulation (EC) No 1272/2008. Although the result is considered to be valid, due to the lack of quality assurance, and very limited documentation, it should be regarded as not being reliable.

Executive summary:

A study was preformed to assess the irritation of the test material to the eye of rabbits. The method followed OECD TG 405.

A single application of 0.1 mL (81 mg) test material was administered to the non irrigated eye of three rabbits. Ocular reactions were recorded 1, 24, 48 and 72 hours after administration.

The test material produced minimal conjunctival irritaiton. All treated eyes appeared normal at the 48-hour observations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation / Corrosion

A single study addressing skin corrosion was available (Pooles, 2004c). The test material was considered not to have the potential to be corrosive to the skin in vivo under the conditions of the study. The study is considered to be relevant.

The TER assay allows the positive identification of corrosive chemical substances, and it further allows the identification of non-corrosive substances and mixtures when supported by a weight of evidence determination using other existing information (e.g. pH, structure activity-relationships, human and/or animal data). It does not provide information on skin irritation, nor does it allow the sub-categorisation of corrosive substances as permitted in the Globally Harmonised System for Hazard Classification and Labelling.

The available data is considered to be relevant and adequate for classification and risk assessment purposes, but not reliable because the study was not performed according to a recognised guideline, nor under GLP, or with sufficient documentation. Although the results are regarded as valid, the endpoint is not considered to be conclusive for skin irritation.

Eye Irritation

Two studies were available addressing eye irritation (Pooles, 2004d and Pooles, 2004e). Pooles (2004d) used the protocol for the rabbit enucleated eye test. This test permits evaluation of undiluted test materials, as they could enter the in-vivo eye test, and hence may be seen advantageous over a number of other in-vitro test systems. The test will not provide information, however, about potential effects of a test material on the conjunctivae, nor about the rate of recovery from an insult. Based on the outcomes of the test the substance was considered unlikely to have the potential to cause severe ocular irritancy in vivo. The study is relevant, but not adequate for classification purposes.

A second study by Pooles (2004e) followed OECD TG 405. A single application of 0.1 mL (81 mg) test material was administered to the non irrigated eye of three New Zealand White rabbits. Ocular reactions were recorded 1, 24, 48 and 72 hours after administration. The test material produced minimal conjunctival irritation. All treated eyes appeared normal at the 48-hour observations.

The study is considered to be relevant and adequate for classification and risk assessment purposes, but not reliable because the study was not performed under GLP, or with sufficient documentation. Although the results are regarded as valid, the endpoint is not considered to be conclusive for eye irritation.

Respiratory Irritation

No data on respiratory irritation was available.

Justification for selection of skin irritation / corrosion endpoint:
Only study available.

Justification for selection of eye irritation endpoint:
The in vivo study provides full information on all the criteria necessary for classification purposes, whereas the in vitro study is only addresses some aspects, and cannot be used to derive a conclusive non-classification.

Justification for classification or non-classification

Skin

The substance was tested with a method comparable to OECD TG 430, and found to be not corrosive to skin. The TER assay allows the positive identification of corrosive chemical substances, and it further allows the identification of non-corrosive substances and mixtures when supported by a weight of evidence determination using other existing information (e.g. pH, structure activity-relationships, human and/or animal data). It does not provide information on skin irritation, nor does it allow the sub-categorisation of corrosive substances as permitted in the Globally Harmonised System for Hazard Classification and Labelling. The substancedoes not meet the criteria for classification as corrosive to the skin according to Directive 2001/59/EC, Annex VI, or classified as irritating to the skin according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.2.2. Because the study is not validated for all classifications, it is not regarded as adequate for classification purposes. In addition the study is not considered reliable. As a result, this endpoint is considered to be not classified, but inconclusive.

 

Eye

An in-vitro study on the eye irritation potential of the test substance was performed by using the protocol for the rabbit enucleated eye test, and found thatthe test substance was unlikely to have the potential to cause severe ocular irritancy in vivo. The second study (Pooles, 2004e), an in vivo OECD TG 405, found the test material produced minimal conjunctival irritation, and all treated eyes appeared normal in the 48-hour observation. As a result, the substance is not considered to be classified according to the criteria set out inDirective 2001/59/EC, Annex VI,or according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.2. Because the in vivo study is not regarded as reliable, this classification is considered to be inconclusive.

 

Inhalation

No data available.