dinotefuran (ISO); 1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21/05/1996 - 09/12/1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(1981)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

(1982)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

EC Number:

605-399-0

Cas Number:

165252-70-0

Molecular formula:

C7H14N4O3

IUPAC Name:

(RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

Test material form:

solid: particulate/powder

Remarks:

powder

Test animals

Species:

mouse

Strain:

other: Crl:CD1[ICR]BR (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Age at study initiation:
- Range finding study: 4 to 8 weeks old
- Definitive study: 4 to 10 weeks old

Weight at study initiation:
- Range finding study: 24.9 to 27.8 g
- Definitive study: 23.0 to 29.6 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration of vehicle: 0.5 % CMC in distilled water
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: no data

Doses:

Range finding study: 500, 1000, 3000, 5000 mg/kg bw
Definitive study: 1000, 2000, 3000 mg/kg bw

No. of animals per sex per dose:

Range finding study: 1 mouse per sex per dose
Definitive study: 5 mice per sex per dose

Control animals:

no

Details on study design:

- Duration of test/exposure period: 14 days
- Rational for dose level selection: The definitive study dose levels were selected based on the results from the range finding study
- Post exposure observation period: 14 days

Statistics:

The LD50 and 95% confidence limits for the individual sexes and the sexes combined were determined by a modified Behrens-Reed-Muench cumulant method.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 450 mg/kg bw

Based on:

test mat.

95% CL:

> 1 801 - < 3 331

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 275 mg/kg bw

Based on:

test mat.

95% CL:

> 1 537 - < 3 369

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 371 mg/kg bw

Based on:

test mat.

95% CL:

> 1 884 - < 2 983

Remarks on result:

other: male and female combined

Mortality:

- In the range-finding study, both animals treated at 5000mg/kg and the male treated at 3000mg/kg died on the day of treatment. All other animals survived the observation period.
- In the main study, deaths occurred at dose levels of ≥2000mg/kg but not at 1000mg/kg (Table 1). All deaths in the main study occurred on the day of treatment.

Clinical signs:

other: Transient clinical signs of toxicity, on the day of treatment only, were apparent at dose levels of ≥2000mg/kg and included hypoactivity, staggering gait, dyspnea, tonic convulsions and tremors.

Gross pathology:

Necropsy and post mortem examination revealed no gross lesions in either decedents or survivors killed at the end of the observation period.

Any other information on results incl. tables

Table 1: Mortality and time of death

Dose level	Number dying / number tested
(mg/kg)	Dose range-finding study		Main study
	Male	Female	Male	Female
500	0 / 1	0 / 1	-	-
1000	0 / 1	0 / 1	0 / 5	0 / 5
2000	-	-	1^a/ 5	2^a/ 5
3000	1^a/ 1	0 / 1	4^a/ 5	4^a/ 5
5000	1^a/ 1	1^a/ 1	-	-

^adied on the day of treatment;

- not tested

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

The acute oral median lethal dose (LD50) and 95% confidence limits were calculated to be 2450 mg/kg and 1801-3331 mg/kg for males, 2275 mg/kg and 1537-3369 mg/kg for females and 2371 mg/kg and 1884-2983 mg/kg for the sexes combined. Therefore, dinotefuran does not require classification according to Reg. (EC) 1272/2008.