Adipohydrazide

Endpoint summary

Description of key information

The acute oral  LD50 to rats of adipic acid dihydrazide is greater than 2000 mg/kg bodyweight. 
The acute inhalation LC50,4h to rats of adipic acid dihydrazide is greater than 5.3 mg/L.

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

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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.

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.

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented, scientifically acceptable study report.

Principles of method if other than guideline:

According to BASF-internal standard.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight at the start of the study: male animals 266 g, female animals 183 gAge at the beginning of the study: 8 weeksThe animals received Kilba A 343 laboratory diet for rats/mice. 10 mm pellets, Klingentalmühle AG, 4303 Kaiseraugst. Switzerland, and drinking water ad libitum during the observation period.The animals were accommodated in fully air-conditioned rooms in which central air-conditioning guaranteed a range of temperature of 20 – 24 °C and a range of relative humidity of 30 - 70%.The rats were housed in groups of five in D III Wire mesh cages, without bedding and with a light/dark rhythm of 12 hours.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged

Details on inhalation exposure:

INA 20 head/nose inhalation system (glass/steel construction, BASF Aktiengesellschaft, V = 55 L), the animals sit in tubes and their snouts project into the inhalation chamber.A dust/air mixture was generated by means of a vibratory metering device (BASF).The substance to be tested was transformed into a dust aerosol by means of a dust generator, and was passed into the inhalation system.An automatic vibrator was used to generate dust. The concentration was adjusted by varying the apertural width and the amplitude of oscillation of the metering beaker.The following flows were adjusted: 1500 L/h of compressed air through the injector and 1500 L/h of conditioned air as dilution air. The supply air was conditioned via a central air-conditioning unit so that there was a temperature of between 19 and 25 °C inside the exposure equipment.The setting of the exhaust air system was 10% lower than that of the supply air system (excess pressure). This ensured that the mixture of the test substance and air was not diluted by laboratory air to the breathing zones of the animals. In order to analyse the particle size, one sample was collected from each test group no earlier than 30 minutes following the start of the study. Prior to sample collection, the impactor was provided with glass fiber collecting disks and a residual particles filter. It was connected to the pump and the test equipment and a sample (9 L) was collectedThe impactor was disassembled, the collecting disks and the residual particles filter were weighed, the samples obtained were analysed gravimetrically. The contents of the preimpactor were also determined gravimetrically.Test atmosphereMMAD (Mass median aerodynamic diameter) / GSD (geometric st. dev .): 3.90 µm / 2.78 µm.The results from particle size analyses demonstrate a fine dust proportion of 85.4 %.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric determination of the concentration

Duration of exposure:

4 h

Concentrations:

5.3 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: The animals surviving the exposure period were observed for 14 days.- Frequency of observations and weighting: The animals' body weights were checked before the start of the study, after 7 days and at the end of the observation period, and were collated in a diagram. The animals were checked for clinical signs on each working day. The lethality was checked daily.- Necropsy of survivors: Subsequent to the 14-day observation period, the animals were sacrificed by means of C02 and subjected to a gross-pathological examination

Statistics:

Yes.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None.

Clinical signs:

other: During exposure: attempts to escape at study start. After exposure: none.

Body weight:

No impairment compared with the control group.

Gross pathology:

Sacrificed animals: nothing abnormal detected.

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The LC50,4h of adipic acid dihydrazide is >5.3 mg/L.

Executive summary:

Rats were exposed to adipic acid dihydrazide as a dust in a head/nose inhalation system to a concentration of 5.3 mg/L. The animals were checked for clinical signs for 14 days. Subsequent to the 14-day observation period, the animals were subjected to a gross-pathological examination.

No mortality and no relevant clinical signs or lesions at post mortem examination were detected. The LC50,4h >5.3 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 300 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
A key study.

Justification for selection of acute toxicity – inhalation endpoint
A key study.

Justification for classification or non-classification

No indications were obtained to justify a classification.