pymetrozine (ISO); (E)-4,5-dihydro-6-methyl-4-(3-pyridylmethyleneamino)-1,2,4-triazin-3(2H)-one

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

15 Jun 1992 to 13 Jul 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Version / remarks:

May 1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)

Version / remarks:

1982

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one

EC Number:

602-927-1

Cas Number:

123312-89-0

Molecular formula:

C10H11N5O

IUPAC Name:

6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one

Test material form:

solid: particulate/powder

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

The content of active ingredient in all samples was found to be in agreement with the nominal concentration. The test article was stable in the vehicle (distilled water) for 5 days at room temperature. During the whole observation period no treatment-related symptoms were observed. Furthermore, signs of local irritation were transient and a dose-response relationship was missing. One female in the 10 mg/kg bw group died, no treatment-related mortality occurred during this study. Bodyweight, food consumption, haematological profile, and blood chemistry parameters investigated were not influenced by the treatment. Organ weights were not affected by the treatment. All macroscopical and microscopical pathology findings were considered to be incidental in nature. In particular, no evidence of dermal toxicity was observed.

Applicant's summary and conclusion

Conclusions:

After topical admistration of the test substance to albino rats, it is concluded that the "no observed effect level" (NOEL) for the test substance in this study is higher than the limit dose of 1000 mg/kg bw.

Executive summary:

In the present study albino rats (Tif: RAif (SPF)) were dermally exposed to 0, 10, 100 and 1000 mg/kg bw per exposure to the test compound. The control group was exposed to vehicle (distilled water) only. Each group consisted of 5 animals per sex. The test article/vehicle suspension was applied under occlusive dressing to the shaved back skin for a period of 4 weeks on a 5 day /week basis. The exposure period was 6 hours per day.The dressings were removed after 6 hours and the application areas were cleaned with lukewarm water.Control analysis of the test article concentration in the vehicle was carried out at all dose levels. The animals were checked for clinical signs and mortality on daily basis. Approximately 17 hours after removing the gauze patches, local skin reactions at the application site of the test article were evaluated according to Draize method. Body weights, food consumption were recorded weekly.Laboratory investigations (haematology, blood chemistry) were carried out on all surviving animals of each dose group at the end of the treatment period. At the end of the test period the surviving controls and treated animals were bled under ether anaesthesia and subjected to detailed autopsy. Organ samples were prepared and subjected to a microscopical examination.

The content of active ingredient in all samples was found to be in agreement with the nominal concentration. The test article was stable in the vehicle (distilled water) for 5 days at room temperature. During the whole observation period no treatment-related symptoms were observed. Furthermore, signs of local irritation were transient and a dose-response relationship was missing. One female in the 10 mg/kg bw group died, no treatment-related mortality occurred during this study. Bodyweight, food consumption, haematological profile, and blood chemistry parameters investigated were not influenced by the treatment. Organ weights were not affected by the treatment. All macroscopical and microscopical pathology findings were considered to be incidental in nature. In particular, no evidence of dermal toxicity was observed.

It is concluded that the "no observed effect level" (NOEL) for the test substance in this study is higher than the limit dose of 1000 mg/kg bw.