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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
(1982)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
1-methyl-2-nitro-3-(tetrahydrofuran-3-ylmethyl)guanidine
EC Number:
605-399-0
Cas Number:
165252-70-0
Molecular formula:
C7H14N4O3
IUPAC Name:
1-methyl-2-nitro-3-(tetrahydrofuran-3-ylmethyl)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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 450 mg/kg bw
Based on:
test mat.
95% CL:
> 1 801 - < 3 331
Sex:
female
Dose descriptor:
LD50
Effect level:
2 275 mg/kg bw
Based on:
test mat.
95% CL:
> 1 537 - < 3 369
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:
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.
Body weight:
Survivors treated at 2000 or 3000mg/kg gained weight throughout the observation period.
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

-

-

1a/ 5

2a/ 5

3000

1a/ 1

0 / 1

4a/ 5

4a/ 5

5000

1a/ 1

1a/ 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.