Adipohydrazide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

adipic dihydrazide

IUPAC Name:

adipic dihydrazide

Constituent 2

Reference substance name:

ADH

IUPAC Name:

ADH

Details on test material:

Names: Adipic dihydrazide; ADHAppearance: White crystalline powderStorage conditions: Room temperature in the darkLot number: 0E96Purity: > 99%Expiry date: 25 May 2012Date received: 04 October 2010

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Healthy nulliparous and non-pregnant female CD (Crl:CD ‘SD’) rats were obtained from Charles River (UK) Ltd.The animals were allocated without conscious bias to cages within the treatment groups. They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.Each animal was assigned an alpha-numeric code and identified uniquely within the study by tail marking. Each cage label was colour-coded and was identified uniquely with the study number, dose level and animal mark.The animals were allowed to acclimatise to the conditions described below for at least 5 days before treatment. For those animals selected for this study, their bodyweights were in the range 197 to 218 g and they were approximately eight to twelve weeks of age prior to dosing (Day 1).Animals were housed inside a barriered rodent facility. The temperature and relative humidity controls were set to maintain the range of 19 to 23°C and 40 to 70% respectively. Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per24 hours. The animals were allowed free access to a standard rodent diet, except for overnight prior to and approximately four hours after dosing.Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.During the acclimatisation period, each cage of animals was provided with a soft white untreated chew block and a plastic shelter for environmental enrichment. The wood blocks were removed from the cage of animals for the same period as the food on the day prior todosing.Each batch of diet was analysed routinely by the supplier for various nutritional components and chemical and microbiological contaminants. Supplier’s analytical certificates were scrutinised and approved before any batch of diet was released for use. The quality of thewater supply is governed by regulations published by the Department for Environment, Foodand Rural Affairs.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1 % methyl cellulose

Details on oral exposure:

The test substance was formulated at a concentration of 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg bodyweight.The test substance formulations were prepared on the day of dosing.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 + 3 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)- Frequency of observations: Cages of rats were checked at least twice daily for any mortalities. - Frequency of weighing: The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weeklybodyweight changes and group mean bodyweights were calculated.- Necropsy of survivors performed: yes/no- Frequency of clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation.All animals were observed for 14 days after dosing.

Statistics:

Not applicable.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at studytermination on Day 15.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The acute median lethal oral dose (LD50) to rats of adipic acid dihydrazide is greater than 2000 mg/kg bodyweight.Adipic acid dihydrazide is included in Category 5 or unclassified, according to the Globally Harmonised System (GHS).

Executive summary:

The study was performed to assess the acute oral toxicity of adipic acid dihydrazide to rats using the Acute Toxic Class method, according to EU- and OECD-methods.

The acute median lethal oral dose (LD50) to rats of adipic acid dihydrazide is greater than 2000 mg/kg bodyweight. Adipic acid dihydrazide is included in Category 5 or unclassified, according to the Globally Harmonised System (GHS).