spirodiclofen (ISO);3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutyrate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.6300 (Developmental Neurotoxicity Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-(2,4-Dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutanoate

Cas Number:

148477-71-8

Molecular formula:

C21H24Cl2O4

IUPAC Name:

3-(2,4-Dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutanoate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar Hannover Crl:WI (Glx/BRL/Han) IGS BR rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Approximately 120 male and 120 female (nulliparous and nonpregnant) were placed on study to provide a minimum of 20 acceptable litters per dietary level. Animals had not been previously treated and were at least 15 weeks (males) or 12 weeks (females) of age at co-housing. The adult males served only as "breeders" and, as such, were not exposed to the test substance or included in any tests. The Wistar rat was selected as the test system due to its general acceptance and suitability for toxicological testing of this type as well as the availability of a historical database.

Administration / exposure

Route of administration:

oral: feed

Results and discussion

Results of examinations

Details on results:

This developmental neurotoxicity study was performed at dietary concentrations of 0, 70, 350 and 1500 ppm. There was no evidence of developmental neurotoxicity in this study.

Applicant's summary and conclusion

Conclusions:

This developmental neurotoxicity study was performed at dietary concentrations of 0, 70, 350 and 1500 ppm. There was no evidence of developmental neurotoxicity in this study.
General
There were no effects on reproduction parameters at any dietary level.
Based on analytical results, the average concentrations of spirodiclofen in the diet were 0,
71.9, 357 and 1452 ppm. The average daily intake of active ingredient was as follows for
nominal concentrations of 0, 70, 350 and 1500 ppm:
Gestation: 0, 6.5, 32.1 and 135.9 mg/kg/day, respectively; and
Lactation: 0, 14.0, 69.7 and 273.8 mg/kg/day, respectively.
Maternal
Compound-related effects consisted of the following:
70 ppm - There were no compound-related effects (NOAEL).
350 ppm - There were no compound-related effects (NOAEL).
1500 ppm - Decreased body weight and food consumption during lactation.
Offspring
Compound-related effects were limited to the following:
70 ppm - There were no compound-related effects (NOAEL).
350 ppm - There were no compound-related effects (NOAEL).
1500 ppm - Decreased body weight and weight gain during lactation, with complete
recovery after weaning.

Executive summary:

Technical-grade spirodiclofen was administered via the diet from gestation day (GD) 0 through lactation day (LD) 21 to mated female Wistar rats, at nominal concentrations of 0, 70, 350 and 1500 ppm. The offspring were evaluated using a functional observational battery, body weight, food consumption, developmental landmarks for sexual maturation, automated measures of activity (figure-eight maze), acoustic startle habituation, learning and memory (passive avoidance and a water maze task), and an ophthalmic examination. Serum cholesterol was measured in the dams and offspring and tissues were collected from the offspring for morphometry (brain) and microscopic examination on PND 21 (brain) and at study termination (brain, an assortment of additional neural tissues and skeletal muscle). In summary, the following observations were noted.

General- There were no effects on reproduction parameters at any dietary level.

Based on analytical results, the average concentrations of spirodiclofen in the diet were 0, 71.9, 357 and 1452 ppm. The average daily intake of active ingredient was as follows for nominal concentrations of 0, 70, 350 and 1500 ppm:

Gestation: 0, 6.5, 32.1 and 135.9 mg/kg/day, respectively; and

Lactation: 0, 14.0, 69.7 and 273.8 mg/kg/day, respectively.

Maternal

Compound-related effects consisted of the following:

70 ppm - There were no compound-related effects (NOAEL).

350 ppm - There were no compound-related effects (NOAEL).

1500 ppm - Decreased body weight and food consumption during lactation.

Offspring

Compound-related effects were limited to the following:

70 ppm - There were no compound-related effects (NOAEL).

350 ppm - There were no compound-related effects (NOAEL).

1500 ppm - Decreased body weight and weight gain during lactation, with complete