thiacloprid (ISO);(Z)-3-(6-chloro-3-pyridylmethyl)-1,3-thiazolidin-2-ylidenecyanamide;{(2Z)-3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Remarks:

Preliminary dose range-finder included in the acute oral neurotoxicity screening study 95-412-GI (please refer to M-000894-03-1 in chapter 7.9.1)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

main study: 29 Jan - 16 Feb 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data provided as summary within an reliable acute oral neurotoxicity screening study; however considered reliable and suitable for assessment of the acute oral toxicity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 1987

Deviations:

yes

Remarks:

only summarized data available

Principles of method if other than guideline:

The present study was intended as dose range-finding study to define the most appropriate dose levels for a further acute oral neurotoxicity screening study. Accordingly, the data referring to the present study are part of the study No. 95-412-GI as available for the acute oral neurotoxicity screening study, included in IUCLID chapter 7.9.1.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-chlor-5-pyridyl-methyl)-cyanimino-1,3-thiazolidin

EC Number:

601-147-9

Cas Number:

111988-49-9

Molecular formula:

C10H9ClN4S

IUPAC Name:

3-(2-chlor-5-pyridyl-methyl)-cyanimino-1,3-thiazolidin

Test animals

Species:

rat

Strain:

other: not specified, but Wistar assumed

Sex:

male/female

Details on test animals or test system and environmental conditions:

No details available from the data source.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No details on the experimental design are available from the data source, however, it is hardly assumed that these were similar to those as described from the main screening study. With respect to the screening study, the test substance was administered by gavage as a single dose in 0.5% methylcellulose-0.4% Tween 80 in deionized water, at a dosing volume of 10 mL/kg bw.

Doses:

27, 36, 85, 244 and 526 mg/kg bw (analytically-confirmed doses)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

None

Statistics:

Not specified

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 85 - < 244 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 0% mortality at 85 mg/kg bw and 100 % mortality at the next dose level of 244 mg/kg bw

Mortality:

27, 36 and 85 mg/kg bw: no deaths occurred in both sexes
244 and 526 mg/kg bw: 100% mortality in both sexes

Clinical signs:

other: 27 mg/kg bw: no clinical signs were observed 36 mg/kg bw: slight repetitive chewing movements (males) 85 mg/kg bw: slight repetitive chewing movements (both sexes), slight tremors (males) and slight oral and nasal stains (female) 244 mg/kg bw: tremors, de

Gross pathology:

No information on gross pathology was provided.

Other findings:

Neurotoxicity:
The time of peak neurobehavioral effects (within the first eight hours following treatment) was estimated to be approximately 4 h following treatment.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The present study was intended as dose range-finding study to define the most appropriate dose levels for a further acute oral neurotoxicity screening study. The data referring to the present study are part of the study No. 95-412-GI, as available for the acute oral neurotoxicity screening study included in IUCLID chapter 7.9.1. The test conduct of the range finding study was in principle similar to OECD TG 401, and analytically-confirmed doses of 27, 36, 85, 244 and 526 mg/kg bw were tested using five rats/sex/dose level. Clinical signs of toxicity were reported, starting from 36 mg/kg bw, which basically consisted of repetitive chewing movements, slight tremors and oral and nasal stains. At the two highest dose levels of 244 and 526 mg/kg bw, the toxic effects further included decreased activity, cool-to-touch body, dilated pupils and clear lacrimation. At 244 mg/kg bw, locomotor incoordination (ataxia) was reported for one female. Clinical signs were generally apparent in both sexes within 2 - 4 h following treatment and recovered in survivors by the following day. Clinical signs were generally comparable for males and females at a given dose level, indicating similar sensitivity for both sexes. With respect to neurotoxicity, it was reported that the time of peak neurobehavioral effects (within the first eight hours following treatment) could be estimated to be approximately four hours following treatment.
Whereas no mortality occurred at doses from 27 to 85 mg/kg bw, 100% mortality was observed at the two highest dose levels of 244 and 526 mg/kg bw, which generally occurred within 24 h after dosing. Thus, a LD50 for acute oral toxicity in the range > 85 - < 244 mg/kg bw is expected. Referring to the CLP classification and labelling criteria (CLP, Annex I), this falls in the range of > 50 - =< 300 mg/kg bw and thus, would trigger a classification for acute oral toxicity as Cat 3 H301.