N,N'-diacetylhydrazine

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw, male/female, rat, similar to OECD 401, Pooles 2004a
Dermal: LD50>2000 mg/kg bw, male/female, rat, similar to OECD 402, Pooles 2004b

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:

supporting study

Study period:

from 2004-03-09 to 2004-03-17

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. Compared to a similar guideline method, a reduced number of animals were tested, a reduced observation period used, and the purity of the test material was not reported. 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 401 (Acute Oral Toxicity)

Deviations:

yes

Principles of method if other than guideline:

A standard test method from the performing test facility was followed. The test was comparable to OECD TG 401. However, only 4 animals were tested and the observation period was only 9 days.

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.

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

No details on test animals and environmental conditions are reported.

Route of administration:

oral: unspecified

Vehicle:

water

Remarks:

The test material was administered orally as a solution in distilled water.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not reported

MAXIMUM DOSE VOLUME APPLIED: not reported

DOSAGE PREPARATION (if unusual): not reported

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 males, 2 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations and weighing:
Weighing: day of dosing, day 1 and day 8
Clinical observations and mortality: 0.5, 1, 2, 4 hours after initiation of exposure, 1, 2, 3, 4, 5, 6, 7, 8 days after initiation of exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were detected.

Individual Body Weight and Weekly Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) Day -1 to Day 8
		Day -1	Day of Dosing	Day 8
2000	1-0 Male	307	290	360	53
	1-1 Male	304	300	382	78
	2-0 Female	203	190	234	31
	2-1 Female	196	182	208	12

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2000 mg/kg bodyweight. 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 study was performed to estimate the toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat.

A group of four fasted animals (two males and two females) was treated with the test material at a dose level of 2000 mg/kg bodyweight. The test material was administered orally as a solution in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths and no signs of systemic toxicity. All animals gained weight during the study and no abnormalities were detected at necropsy. The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Although the result is considered to be scientifically valid, due to the lack of GLP, limited documentation, deviations, and the lack of purity information, it must be regarded as not reliable.

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:

supporting study

Study period:

from 2004-03-09 to 2004-03-17 (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. Compared to a similar guideline method, a reduced number of animals were tested, a reduced observation period used, and the purity of the test material was not reported. 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 402 (Acute Dermal Toxicity)

Deviations:

yes

Principles of method if other than guideline:

A standard test method from the performing test facility was followed. The test was comparable to OECD TG 402. However, only 4 animals were tested and the observation period was only 9 days.

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.

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

No details on test animals and environmental conditions are reported.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE: intact skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 males, 2 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations and weighing:
Weighing: day of dosing, day 1 and day 8
Clinical observations and mortality: 0.5, 1, 2, 4 hours after initiation of exposure, 1, 2, 3, 4, 5, 6, 7, 8 days after initiation of exposure
Dermal reaction: 1, 2, 3, 4, 5, 6, 7, 8 days after initiation of exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality, body weight, dermal reactions

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity or dermal irritation were noted.

Gross pathology:

No abnormalities were detected.

Individual bodyweights and weekly bodyweight changes

Dose Level mg/kg	Animal number and sex	Bodyweight (g) at day			Bodyweight change day 1 to day 8
		Day 1	Day of dosing	Day 8
2000	1-0 male	215	231	296	81
	1-1 male	231	240	303	72
	2-0 female	218	216	244	26
	2-1 female	206	212	232	26

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat strain was found to be greater than 2000 mg/kg bodyweight. 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 study was performed to estimate the toxicity of the test material following a single dermal administration in the Sprague-Dawley CD strain rat.

A group of four animals (two males and two females) was given a single, 24-hour, semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. No signs of systemic toxicity or dermal irritation were noted. 3 out of 4 animals lost weight from the day of dosing to day 1 but alll animals gained weight from the day of dosing to day 8. At necropsy, no abnormalities were detected. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat strain was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Although the result is considered to be scientifically valid, due to the lack of GLP, limited documentation, deviations, and the lack of purity information, it must be regarded as not reliable.

Additional information

Oral

Only one study is available for acute oral toxicity (Pooles, 2004a). A standard screening test method from the performing test facility was followed, comparable to an OECD TG 401. In the oral study, a group of four fasted animals (two males and two females, Sprague-Dawley CD strain rat) were treated with the test material at a dose level of 2000 mg/kg bodyweight. The test material was administered orally as a solution in distilled water and the animals were observed for 8 days. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. Only 4 animals were tested and the observation period was only 9 days, the study was not conducted under GLP, the test material purity was not reported, and very limited documentation was presented. There were no deaths and no signs of systemic toxicity and all animals gained weight during the study and no abnormalities were detected at necropsy.

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. The endpoint is not considered to be conclusive.

 

Dermal

Only one study is available for acute dermal toxicity (Pooles, 2004b). A standard screening test method from the performing test facility was followed. The test was comparable to OECD TG 402. In the dermal study, a group of four fasted animals (two males and two females, Sprague-Dawley CD strain rat) were treated with the test material at a dose level of 2000 mg/kg bodyweight. The test material was administered dermally with a single, 24-hour, semi-occluded dermal application of the test material to intact skin, and the animals were observed for 8 days. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. Only 4 animals were tested and the observation period was only 9 days, the study was not conducted under GLP, the test material purity was not reported, and very limited documentation was presented. There were no deaths. No signs of systemic toxicity or dermal irritation were noted. 3 out of 4 animals lost weight from the day of dosing to day 1 but all animals gained weight from the day of dosing to day 8. At necropsy, no abnormalities were detected.

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. The endpoint is not considered to be conclusive.

 

Inhalation

No study available

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Oral

No observations of toxicity were reported for the test substance via the oral route at the limit dose. Therefore, the substance does not meet the criteria for classification according to Directive 2001/59/EC, Annex VI, 3.2.1-3.2.3. However, because the available data is not considered reliable, the classification is not considered conclusive.

 

No observations of toxicity were reported for the test substance via the oral route at the limit dose. Therefore, the substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1 as amended by Regulation (EC) No. 286/2011. However, because the available data is not considered reliable, the classification is not considered conclusive.

 

Dermal

No observations of toxicity were reported for the test substance via dermal route at the limit dose. Therefore, the substance does not meet the criteria for classification according to Directive 2001/59/EC, Annex VI, 3.2.1-3.2.3. However, because the available data is not considered reliable, the classification is not considered conclusive.

 

No observations of toxicity were reported for the test substance via dermal route at the limit dose. Therefore, the substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1 as amended by Regulation (EC) No. 286/2011. However, because the available data is not considered reliable, the classification is not considered conclusive.

 

Inhalation

No data available.