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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 19-June 2, 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reference substance 001
Cas Number:
N/A
Molecular formula:
C10H16O2
Test material form:
liquid
Remarks:
Colorless
Details on test material:
Test substance was expected to be stable for the duration of testing.
Specific details on test material used for the study:
- lot number of test material:
CH-DA-01-18

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Stored refrigerated

- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage:
Test substance was expected to be stable for the duration of testing.

- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis:
The test substance was applied as received

- Solubility and stability of the test material in the solvent/vehicle and the exposure medium:
The test substance was applied as received

TREATMENT OF TEST MATERIAL PRIOR TO TESTING

- Treatment of test material prior to testing (e.g. warming, grinding):
Mixed well prior to use

- Preliminary purification step (if any):
None

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 10 weeks
- Weight at study initiation: 330-3 59 grams and females 222-245 grams
- Housing:
The animals were housed in caging which conforms to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Animals were group housed, except on the day of application, at which time they were singly housed until the animals were deemed acceptable, based on observations, to return to group housing. Enrichment (e.g., toy) was placed in each cage and litter was changed at least once per week.

- Diet (e.g. ad libitum):
Envigo Teklad Global 16% Protein Rodent Diet® #20 16. The diet was available ad libitum.

- Water: Filtered tap water was supplied ad libitum

- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 34 - 68
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 2 inches x 3 inches
- % coverage: approximately 10% of the body surface
- Type of wrap if used: 3-inch Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing: 3% soap solution followed by tap water and a clean paper towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 5000 mg/kg bw
- Concentration (if solution): applied as received

VEHICLE
No vehicle. Substance applied as received.
Duration of exposure:
24 hours
Doses:
- other: 5000 mg/kg bw
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration:
14 days post exposure

- Frequency of observations and weighing:
observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application, after patch removal, and then at least once daily thereafter for 14 days. Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (terminal).

- Necropsy of survivors performed:
yes

- Clinical signs including body weight
gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

- Other examinations performed:
Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
Limited to the calculation of the mean density value for dosing.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality up to the highest dose tested.
Mortality:
No mortalities
Clinical signs:
No clinical signs
Body weight:
All animal gained body weight
Gross pathology:
No signs of gross toxicity
Other findings:
No signs of dermal irritation, adverse clinical effects, or abnormal behavior.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the single dose acute dermal LD50 of Dihydronepetalactone is
greater than 5000 mg/kg of body weight in male and female rats.
Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for Dihydronepetalactone to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 5000 mg/kg of body weight in male and female rats.



Five thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application (initial) and again on Days 7 and 14 (terminal). Necropsies were performed on all animals at terminal sacrifice.


 


All animals survived test substance administration, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse clinical effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

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