Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 April 2012 to 16 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
944127-07-1
IUPAC Name:
944127-07-1
Test material form:
other: solid (unspecified)
Details on test material:
- Appearance: White Solid
- Storage conditions of the test material: Ambient (18 to 36 °C)
- pH of test material: 4.60

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Males: 260.29 to 294.73 g; Females: 203.13 to 210.10 g. Weight variation did not exceed ± 20 % of the mean weight for each sex.
- Fasting period before study: No
- Housing: Rats were housed individually in standard polysulfone cages (Size: approximately 425 mm long x 266 mm deep x 175 mm high), with stainless steel top grills having facilities for pelleted food and drinking water. Steam sterilised clean corn cob bedding was used and changed along with the cage twice weekly. The rats were provided with huts as environmental enrichment in each cage during the experimental period.
- Diet (e.g. ad libitum): Standard rat and mouse pelleted maintenance diet was provided ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in a water filter-cum-purifier was provided to animals ad libitum in polycarbonate bottles with stainless steel sipper tubes. The water in the bottles was replenished once daily and the water bottles were changed once a week.
- Acclimation period: Five days for the females and seven days for the males under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 65 to 67 % (relative)
- Air changes (per hr): 12 to 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours of light and 12 hours of dark

IN-LIFE DATES: From: 25 April 2012 To: 16 May 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
The test material was made into a paste with Milli-Q water.
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsolateral thoracic surface. Approximately 24 hours prior to treatment, the hair on the skin was clipped (approximately 8 x 10 cm) with an electric clipper.
- % coverage: About 10 % of the body surface of each animal.
- Type of wrap if used: The test material was applied on 6 ply cotton gauze patches (males: 9 x 6 cm; females: 8 x 5 cm). The patch was secured in position by non-allergenic surgical tape wound around the torso.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The tape and patches were removed and the application sites were wiped with water and clean towels to remove any residual test material.
- Time after start of exposure: After the 24 hour contact period.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight.
- For solids, paste formed: Yes, with Milli-Q water.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 to 0.7 mL.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following application: 14 days following test material application.
- Frequency of observations and weighing: The animals were observed five times on test day 1 (day of application), at 30 minutes, 1, 2, 3 and 4 hours after dose application and once daily during days 2 to 15. Individual body weights of animals were recorded on test day 1 (pre-application), day 8 (7 days post application) and day 15 (14 days post application). The site of application was observed for local skin reactions once daily during the 14 day observation period.
- Necropsy of survivors performed: Yes. All animals were necropsied at the end of the 14 day observation period; animals were sacrificed by exsanguination under isoflurane anaesthesia. External surfaces of the body, all orifices, tissues and organs of the thoracic and abdominal cavities of all animals were examined. All necropsy observations were recorded.

Results and discussion

Preliminary study:
The limit test at 2000 mg/kg was initiated with five female rats. As there was no test material-related mortality, five male rats were tested at the same dose.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality. All animals exposed to the limit dose survived.
Clinical signs:
There were no clinical signs of toxicity in any animal.
Body weight:
All the rats gained body weight throughout the 14-day observation period. Values are reported in Table 1.
Gross pathology:
There were no abnormalities detected at necropsy.
Other findings:
There were no skin reactions observed at the site of application.

Any other information on results incl. tables

Table 1: Body Weight and Body Weight Changes

Sex

Rat Number

Body weight (g)

Initial

Day 8

Weight change

(Day 8 - Initial)

Day 15

Weight change

(Day 15 - Initial)

F

Rm851

203.13

209.32

6.19

217.38

14.25

Rm852

205.03

209.19

4.16

215.10

10.07

Rm853

210.10

217.11

7.01

227.35

17.25

Rm854

207.86

216.19

8.33

221.15

13.29

Rm855

203.18

213.28

10.10

222.71

19.53

M

Rm856

291.41

310.86

19.45

335.79

44.38

Rm857

277.34

290.75

13.41

312.01

34.67

Rm858

265.63

277.19

11.56

289.48

23.85

Rm859

260.29

276.13

15.84

289.92

29.63

Rm860

294.73

317.33

22.60

338.14

43.41

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute dermal LD50 was >2000 mg/kg bodyweight in male and female Wistar strain rats and the test material requires no classification in accordance with EU criteria.
Executive summary:

The acute dermal toxicity potential of the test material to male and female Wistar strain rats was assessed in accordance with the standardised guidelines OECD 402 and US EPA OPPTS 870.1200 under GLP conditions.

The study was initiated with a limit test at 2000 mg/kg in five female rats. The test material was made into a paste with Milli-Q water and administered as a single dermal dose to the clipped dorsolateral thoracic surface. As no mortality, local skin reactions or clinical signs were observed, the test material was similarly administered to five male rats.

Rats were observed for 14 days post treatment. All animals were sacrificed as scheduled on study Day 15 and subjected to gross necropsy.

There were no clinical signs of toxicity and none of the animals died. No local skin reactions were observed and all the animals gained body weight during the 14-day observation period. There were no gross abnormalities detected in any of the rats at necropsy.

Under the conditions of this study, the acute dermal LD50 was determined to be >2000 mg/kg bodyweight in male and female Wistar strain rats, indicating the test material requires no classification in accordance with EU criteria.