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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 May 2018 - 29 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
(SPF Caw)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 226.7 g (SD = 26.1 g)
- Fasting period before study: not specified.
- Housing: During the treatment, the animals were kept in individual cages. On D1, the animals were put together into their cage. The rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains dust free wood shavings which were changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet (e.g. ad libitum): Ad libitum. Teklad Global 16% Protein Rodent Diet (ENVIGO 2016).
- Water (e.g. ad libitum): Ad libitum. Drinking water (tap-water from public distribution system). Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE).
- Acclimation period: the animals were acclimatized for at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC to 25ºC
- Humidity (%): 30 to 70%
- Air changes (per hr): >10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light (07.00 to 19.00) and 12 hours dark cycle.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: at least 10% of the body surface area.
- Type of wrap if used: porous gauze dressing (50 mm x 50 mm non-woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic microporeTM adhesive tape from 3M).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.26 mL/kg body weight
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A
Duration of exposure:
24 h
Doses:
Range finding study: 2000 mg/kg body weight
Main study: 2000 mg/kg body weight
No. of animals per sex per dose:
Range finding study: 1 female per dose
Main study: 2 females per dose
Control animals:
yes
Remarks:
(study performed on three females receiving distilled water by topical application under requirements of OECD Guideline 402)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At each step, the animals were observed three times on test day 0 (day of administration), i.e. at T0+30 min, T0+3h and T0+5h, and once daily during days 1 to 14 post administration. The body weights were recorded on test day 0 (just before administration) then on D2, D7, and D14.
- Necropsy of survivors performed: yes. At termination, gross pathological findings were recorded and reported.
- Other examinations performed:
Clinical observations: spontaneous activity, Preyer’s reflex (noise), respiratory rate, convulsions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex and treatment site (erythema, dryness of the skin, scab, etc.)

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
Erythema was noted in treated animals (2/3) at 48 hours post dose and was totally reversible on day 6.
Scab was noted in treated animals (2/3) between days 6 and 7.
Dryness of the skin was noted in treated animals (2/3) between days 7 and 10.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopic examination of the animal at the end of the study did not reveal treatment-related changes.

Any other information on results incl. tables

Table 1: Body weight and weight gain in grams

Females

D0

D2

D2-D0

D7

D7-D0

D14

D14-D0

Rf 2516

200

221

21

240

40

271

71

Rf 2570

231

236

5

243

12

269

38

Rf 2571

229

241

12

254

25

278

49

MEAN

220.0

232.7

12.7

245.7

25.7

272.7

52.7

SD

17.3

10.4

8.0

7.4

14.0

4.7

16.8

Applicant's summary and conclusion

Interpretation of results:
other: No category (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.

Executive summary:

The acute dermal toxicity of the test item was studied according to OECD Guideline 402 (GLP study). 3 female Sprague-Dawley rats were tested for a exposure period of 24 h. Initially, a range finding study was conducted at a single dose of 2000 mg/kg bw in one animal. Based on the results of this preliminary two additional rats were tested at a dose of 2000 mg/kg bw. No mortality was observed. The body weight evolution of the animals remained normal during the study. Erythema was noted in treated animals (2/3) at 48 hours post dose and was totally reversible on day 6. Scab was noted in treated animals (2/3) between days 6 and 7. Dryness of the skin was noted in treated animals (2/3) between days 7 and 10. No other clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. Based on these results, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.