Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 15th to November 29th, 2016.
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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
(SPF Caw)
Sex:
male/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: the males were 7 weeks old and the females 8 weeks old.
- Weight at study initiation: the mean weight of male rats was 273.8 g, and the mean weight of female rats 217.2 g.
- Housing: during the treatment, animals were kept in individual cages. They were solid-bottomed clear polycarbonate cages with a stainless steel mesh lid, containing dust free weed shavings (changed at least 2 times per week).
- Diet (e.g. ad libitum): foodstuff (ENVIGO 2016) ad libitum.
- Water (e.g. ad libitum): tap-water from public distribution system ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 15/11/2016 To:29/11/2016.

Administration / exposure

Type of coverage:
other: non-occlusive
Vehicle:
DMSO
Details on dermal exposure:
TEST SITE
- Area of exposure: at least 10% of the body surface area
- % coverage: at least 10% of the body surface area
- Type of wrap if used: non-occlusive porous gauze dressing (50x50 mm2 non-woven swab, 4-layer patch, MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic micropore™ adhesive tape from 3M).

REMOVAL OF TEST SUBSTANCE
- Washing: the gauze dressings were removed and the treated area was rinsed with distilled water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 0.2 g/ml
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes
Remarks:
control group referred to historical values.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, the animals were weighed on day 0 (just before administering the test item) then on day 2, day 7, and day 14.
- Necropsy of survivors performed: yes. Observed organs: oesophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, testicles, adrenals, pancreas. As no abnormalities were observed, no microscopic examinations were performed.
- Other examinations performed: clinical signs, body weight. Histopathological examination was not performed because no macroscopic anomalies were observed in any organ.

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 mortality occurred during the study.
Clinical signs:
No systemic clinical signs related to the administration of the test item were observed. Erythema was noted in all animals (10/10) at 24h post-dose; it was totally reversible at day 3. Dryness of the skin was noted in females at day 2 and in all animals at day 3. The skin recovered a normal aspect on day 4. Yellow coloration was noted in all animals at 24h post-dose.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopic examinations of the animals at the end of the study did not reveal treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
EU criteria.
Conclusions:
The dermal LD50 of the test item in rats is greater than 2000 mg/kg bw.
Executive summary:

To determine the acute dermal toxicity of the test item in rats, a limit test was performed, according to OECD 402 (GLP study). The test item was applied onto the intact skin of 10 Sprague Dawley rats (5 males, 5 females) at a dose of 2000 mg/kg bw. All animals were observed once daily for 14 days, survival and body weight were monitored. There were no mortality, adverse clinical signs, abnormal changes in body weights or macroscopic findings. Therefore, the test item was found to be non-toxic by dermal route, with an LD50 > 2000 mg/kg bw in rats.