1,3-Propanediaminium, 2-hydroxy-N1,N1,N1,N3,N3-pentamethyl-N3-[3-[(2-methyl-1-oxo-2-propen-1-yl)amino]propyl]-, chloride (1:2)

Endpoint summary

Description of key information

Oral LD50 in rat: > 2000 mg/kg bw (OECD 423 and GLPs compliant study)

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:

From 10 November 2015 to 08 February 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: CY50561001
- Expiration date of the batch: 24/04/2016
- Purity test date: 65.4%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature 15-25°C, below 70 RH%
- Solubility and stability of the test substance in the solvent/vehicle: soluble in water. Stability not checked

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was freshly formulated at a concentration of 200 mg a.i/mL in the vehicle (distilled water)
- Final dilution of a dissolved solid, stock liquid or gel: 200 mg a.i/mL

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
- Weight at study initiation: 11 weeks old
- Fasting period before study: On the night before treatment
- Housing: LIGNOCEL ¾ S certified wooden chips (Brandenburg Holzfaserstoffe GmbH & Co. KG, Arkeburger Str. 31, G-49424, Goldenstedt) were available to animals during the study. Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 26, 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 – 22.2°C
- Humidity (%): 35 - 62 %
- Air changes (per hr): 15 – 20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 10 November 2015 To: 25 November 2015

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg a.i/L. Purity conversion has been applied in the study (for this purpose, the 65.4% purity value of the substance was taken into consideration).
- Justification for choice of vehicle:
- Lot/batch no. (if required): 6820914
- Purity: N/A

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual):The test item was freshly formulated at a concentration of 200 mg a.i/mL in the vehicle, in the Pharmacy of CiToxLAB Hungary Ltd. on the day of administration. The formulation container was stirred continuously up to the end of dose administration procedures.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw of Diquat

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter
- Necropsy of survivors performed: Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Statistics:

N/A

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

Diquat did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: Acute oral administration of Diquat did not cause any test item related effect.

Gross pathology:

At necropsy, no macroscopic findings were reported at a dose level of 2000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Diquat was found to be above 2000 mg/kg bw in female CRL:(WI) rats. According the GHS criteria, Diquat can be ranked as “Unclassified” for acute oral exposure as no treatment-related mortality or clinical signs were reported at the tested dose of 2000 mg/kg bw.

Executive summary:

The single-dose oral toxicity of Diquat was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in CRL:(WI) rats.

Two groups of 3 female CRL:(WI) rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in distilled water at a concentration of 200 mg a.i/mL at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination.

The results of the study were summarized as follows:

Diquat did not cause mortality at a dose level of 2000 mg/kg bw.

Acute oral administration of Diquat did not cause any test item related clinical signs.

There were no effects on body weights or body weight gains that could be attributed to treatment with Diquat.

At necropsy, no macroscopic findings were reported at a dose level of 2000 mg/kg bw.

In conclusion, under the conditions of this study, the acute oral LD50 value of the test item Diquat was found to be above 2000 mg/kg bw in female CRL:(WI) rats.

According to the GHS criteria, Diquat can be ranked as "Unclassified” for acute oral exposure as no treatment-related mortality or clinical signs were reported at the tested dose of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Study fully reliable (GLP and OECD 423 compliant).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study performed according to OECD Test guideline 423 and in compliance with GLP, two groups of 3 female CRL:(WI) rats were treated with the test item at a dose level of 2000 mg/kg bw at a dose volume of 10 mL/kg bw.

Diquat did not cause mortality at a dose level of 2000 mg/kg bw. Acute oral administration of Diquat did not cause any test item related clinical signs up to the end of the 14 -day observation period. There were no effects on body weights or body weight gains that could be attributed to treatment with Diquat.

At necropsy, no macroscopic findings were reported at a dose level of 2000 mg/kg bw.

In conclusion, under the conditions of this study, the acute oral LD50 value of the test item Diquat was found to be above 2000 mg/kg bw in female CRL:(WI) rats.

Justification for classification or non-classification

Under the conditions of this study, the acute oral LD50 value of the test item Diquat was found to be above 2000 mg/kg bw in female CRL:(WI) rats.

According to the GHS criteria, Diquat can be ranked as “Unclassified” for acute oral exposure as no treatment-related mortality or clinical signs were reported at the tested dose of 2000 mg/kg bw.