Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 August 2017 - 13 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)
Version / remarks:
November 2000, including the most recent revisions.
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical appearance: pale yellow liquid
- Storage conditions: at room temperature
Specific details on test material used for the study:
- No correction factor for purity was required.
- pH (1% in water, indicative range): 4.09 – 3.70
- Density: 1.113 g/cm^3

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant:yes
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: males: 264-298 g; females: 174-208 g.
- Fasting period before study: no
- Housing: Group housing (up to 5 animals of the same sex together) on arrival and individual housing during the study. Polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust were used.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum throughout the study, except during designated procedures.
- Water: Municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18-24 (actual: 21-22)
- Humidity (%): 40-70 (actual: 49-72)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 August 2017 To: 13 September 2017

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm^2 for males, 18 cm^2 for females
- % coverage: 10% of the total body surface
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 5000 mg/kg bodyweight
- Constant volume or concentration used: yes
Duration of exposure:
24 hours (1 animal exposure between 7 and 22 hours)
Doses:
The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg bw) / spec.gravity or density (g/mL).
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality: twice daily; Clinical observations: at periodic intervals on the day of dosing (at least three times) and once daily thereafter; Body weights: on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
- Hunched posture, shallow respiration, piloerection and/or chromodacryorrhoea (snout) were noted for the animal between day 1 and day 3.
- Scabs (back and left flank), scales (back), focal erythema (back and left flank) and/or general erythema (back, neck and left flank) were noted for several animals during the observation period. Maculate erythema, brown discoloration and/or scales were seen in the treated skin-area of several animals during the observation period. These local effects were considered not to have affected the conclusion of the study.
Body weight:
The mean body weight gain during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study, performed according to OECD guideline 402 and GLP principles, the dermal LD50 value of X-19657 in Wistar rats was established to exceed 5000 mg/kg body weight. Based on this result, the test item is not classified for acute toxicity according to GHS and Regulation (EC) No. 1272/2008.