Diquat dibromide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan 1990 to Mar 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diquat dibromide

EC Number:

201-579-4

EC Name:

Diquat dibromide

Cas Number:

85-00-7

Molecular formula:

C12H12N2.2Br

IUPAC Name:

1,1'-ethylene 2,2'-bipyridyldiylium dibromide

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Alpk:APfSD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 - 10 weeks old males and 7 - 11 weeks old females
- Weight at study initiation: 243 - 356 g males and 180 - 240 g females
- Fasting period before study: overnight for a period of 16 to 24 hours
- Housing: housed in suspended cages (37 cm length x 32 cm width x 20 cm height). The floor and the back of each cage were made of 1.2 cm square stainless steel mesh. The sides were made of solid stainless steel and the front was made of polycarbonate. A maximum of five rats were housed in each cage and the sexes were kept separately
- Diet: Parton Combined Diet, ad libitum
- Water: water via an automatic system, ad libitum
- Acclimation period: minimum of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 24
- Humidity (%): 50 ± 10
- Air changes (per hr): 20 - 30
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

dionised

Details on oral exposure:

The test substance was administered at a dose volume of 10 mL/kg bw

Doses:

100, 150, 200, 225 and 250 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Animals were observed for signs of systemic toxicity once within 2 hours of dosing and again between 4 and 7 hours after dosing. Subsequent observations were made once daily, or twice daily whenever there were significant signs of toxicity.
- The animals were weighed on the day before dosing (day-1), the day of dosing (day 1) and on susequent days thereafter.
- All animals were necropsied and examined microscopically.

Statistics:

The acute oral LD50 was calculated from the mortality data (which included animals that were killed in extremis) by logistic regression using nominal dose values. Confidence limits were calculated using a likelihood ratio interval.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

214 mg/kg bw

Based on:

test mat.

95% CL:

>= 180 - <= 271

Remarks on result:

other: Original value presented in study

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

222 mg/kg bw

Based on:

test mat.

95% CL:

>= 203 - <= 241

Remarks on result:

other: Original value presented in study

Effect levels 3

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

400 mg/kg bw

Based on:

test mat.

95% CL:

>= 336 - <= 506

Remarks on result:

other: Recalculated value, expressed as pure substance, see ‘Any other information on results incl. tables’ for respective calculation

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

415 mg/kg bw

Based on:

test mat.

95% CL:

>= 379 - <= 450

Remarks on result:

other: Recalculated value, expressed as pure substance, see ‘Any other information on results incl. tables’ for respective calculation

Mortality:

Following a single oral dose of 100 mg/kg bw, no signs of toxicity were seen and none of the animals died. One male animal was found dead following a dose of 150 mg/kg bw and one male animal and one female animal were killed in extremis following a dose of 200 mg/kg bw. Of the animals dosed with 225 mg/kg bw two male animals and two female animals were either killed in extremis or found dead by day 8, surviving animals had recovered by day 12. All animals dosed with 250 mg/kg were either killed in extremis or found dead by day 5.

Clinical signs:

other: Following a dose of 100 mg/kg, there were no signs of toxicity. At 150 and 250 mg/kg, signs of toxicity were seen including decreased activity, hypothermia, piloerection, reduced splay reflex, distended abdomen, sides pinched in, ungroomed, upward curvatu

Gross pathology:

Two female animals dosed at 225 mg/kg bw had stomach and/or intestines filled with gas. One of these animals had pale kidneys and intrapelvic dilatation of the right kidney. The other animal had mottled kidneys. One male animal dosed at 250 mg/kg bw had stomach and intestines filled with gas.

Any other information on results incl. tables

Calculation of key result

The original effect levels were expressed as cation species of the registered substance. The key effect levels are re-calculated and corrected to include the counterion species by multiplying with 1.868 (344.0 g/mol molecular weight of registered substance divided by 184.2 g/mol molecular weight of cation species):

The acute oral LD50 for male rats: 1.868 x 214 = 400 mg registered substance /kg bw.

The acute oral LD50 for female rats: 1.868 x 222 = 415 mg registered substance /kg bw.

Table 1 Analysis of test substance

Nominal Concentration test substance (mg/mL)	Mean Analysed Concentration test substance (mg/mL)
10	10.2
15	15.0
20	20.3
22.5	23.0
25	25.2

Table 2 Cumulative mortality data

Day No	Dose (mg/kg) and Cumulative Mortality
	100	150	200	225	250
Male
2	0/5	0/5	0/5	0/5	1/5
3	0/5	0/5	0/5	1/5	1/5
4	0/5	1/5	0/5	2/5	4/5
5	0/5	1/5	0/5	2/5	5/5
6	0/5	1/5	1/5	2/5	5/5
15	0/5	1/5	1/5	2/5	5/5
Female
3	0/5	0/5	0/5	0/5	2/5
4	0/5	0/5	0/5	0/5	3/5
5	0/5	0/5	1/5	0/5	5/5
6	0/5	0/5	1/5	1/5	5/5
8	0/5	0/5	1/5	2/5	5/5
15	0/5	0/5	1/5	2/5	5/5

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 was 214 mg/kg bw test substance ion for male rats (95 % confidence limits, 180 - 271 mg/kg bw) and 222 mg/kg bw test substance ion for female rats (95 % confidence limits, 203-241 mg/kg bw).
This is equivalent to an acute oral LD50 of 400 mg/kg bw test substance salt for male rats (95 % confidence limits, 336 - 506 mg/kg bw) and 415 mg/kg bw test substance salt for female rats (95 % confidence limits, 379 - 450 mg/kg bw) of the registered substance.

Executive summary:

In this GLP compliant acute oral toxicity study, comparable to OECD guideline 401, groups of five male and five female Wistar rats each received a single oral dose of test substance technical (purity 21.1% w/w test substance ion) in deionised water at levels of 100, 150, 200, 225 or 250 mg test substance ion/kg bw and were observed up to 15 days. The animals were assessed daily for any signs of toxicity and their body weights were recorded at intervals.

Following a single oral dose of 100 mg/kg bw, no signs of toxicity were seen and none of the animals died. One male animal dosed at 150 mg/kg bw and one male and one female animal dosed at 200 mg/kg were either found dead or killed in extremis. Surviving animals at these two dose-levels showed signs of slight to moderate toxicity which persisted until day 7. Signs of extreme toxicity were seen in all animals dosed with 225 or 250 mg/kg bw. Two male and two female animals dosed with 225 mg/kg bw were either killed in extremis or found dead by day 8, although the surviving animals recovered by day 12. All animals dosed with 250 mg/kg bw were either found dead or killed in extremis by day 5.

The acute oral LD50 was 214 mg/kg bw test substance ion for male rats (95 % confidence limits, 180 - 271 mg/kg bw) and 222 mg/kg bw test substance ion for female rats (95 % confidence limits, 203-241 mg/kg bw). This is equivalent to an acute oral LD50 of 400 mg/kg bw test substance salt for male rats (95 % confidence limits, 336 - 506 mg/kg bw) and 415 mg/kg bw test substance salt for female rats (95 % confidence limits, 379 - 450 mg/kg bw) of the registered substance.