Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 January 2017 - 11 April 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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
yes
Remarks:
see 'Principles of method if other than guideline'.
Principles of method if other than guideline:
Occlusive coverage was used instead of semi-occlusive coverage (as recommended in OECD guideline 402).
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Appearance: colourless or light yellow viscous liquid
Storage conditions: at room temperature, container tightly closed, flushed with nitrogen.

Test animals

Species:
rat
Strain:
other: Crl: CD(SD), SPF animal
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Atsugi Breeding Center, Japan
- Age at study initiation: 7 weeks old
- Weight at study initiation: males: 251-284 g, females: 204-239 g
- Housing: polycarbonate flat-bottomed cages (W260 x D420 x H180 mm) with pulp bedding
- Diet: Pellet diet MF (Lot No. 161021; Oriental Yeast Co., Ltd.) was offered ad libitum
- Water: municipal tap water filtered through a 5-µm cartridge filter and sterilized with an ultraviolet sterilizer was offered ad libitum through an automatic water-supply system.
- Acclimation period: for 6 days after receipt

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.3°C - 24.7 °C
- Humidity (%): 35.8% - 63.2%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 January 2017 To: 1 February 2017

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Remarks:
(Sigma-Aldrich Corp.; Lot No. U5429)
Details on dermal exposure:
TEST SITE
- Area of exposure: 4 cm x 5 cm
- Application method: dosing material impregnated into a piece of lint was applied to the application site occlusively with non-permeable adhesive tape for 24 hours. It was secured with stretch adhesive bandage for contact improvement.

REMOVAL OF TEST SUBSTANCE
- Washing: after patch removal with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 10 mL/kg body weight
- Constant volume or concentration used: yes

VEHICLE
- Amount applied: 8.003 g of test substance in 40 mL corn oil
- Concentration: 20-w/v%
- Lot no.: U5429
- Purity: not indicated
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (general condition): On day 0: within 30 minutes of application, and subsequently at 1,2,3,4, and 6 hours after initiating application. On the following days (day 1-14) observations were performed daily.
- Frequency of weighing: Before application, on the day of application (day 0) and on day 1, 2, 3, 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No male or female died in either the control or test substance group.
Clinical signs:
No abnormalities were noted in either sex for the control group as well as for the test-substance group.
Body weight:
Test-substance group: the body weights decreased as follows: 4 males 1 day after application (-12 through -2 g), all females 1 day after application (-8 through -1 g), and 2 females 2 days after application (-14 through -7 g). However, the weights shifted to increase by 3 days after application, and this increase was satisfactory. The gain for 14 days ranged from 103 through 145 g in males and from 23 through 41 g in females.
Control group: the body weights of all animals decreased 1 day after application (male: -7 through -1 g; female -12 through -1 g). However, the increase from 2 days after application was satisfactory. The weight gain for 14 days ranged from 68 through 136 g in males and from 31 through 47 g in females.
Gross pathology:
No abnormalities were noted in either sex in the control group as well as in the test-substance group.
Other findings:
There was no indication of skin irritation up to the relevant limit dose level.

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 acute dermal LD50 of STABiO D-376N was found to exceed 2000 mg/kg body weight. Based on these findings, the substance is not classified under GHS.
Executive summary:

In an acute dermal toxicity study, performed according to OECD guideline 402 and GLP principles, STABiO D-376N was tested in 5 female and 5 male rats per dose group. Both the control and the test-substance groups consisted of 5 each of female and male. The test material was prepared as a 20 w/v% formulation, using corn oil as a vehicle. The study was conducted at a limit dose of 2000 mg/kg body weight. The test material was applied occlusively for 24 hours. Mortality and general condition were monitored for 14 days after application. No female or male died in either group and no abnormalities were noted during the in-life phase and during gross pathology. Body weights increased satisfactory after decreasing in the first 3 days after application (test-substance group), and the gain for the 14 day period was normal. Based on these results, the LD50 was determined to be >2000 mg/kg body weight and STABiO D-376N is not classified under GHS.