Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from September 25th to October 10th, 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)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: EPA OPPTS 870.1000 (Acute Toxicity Testing - Background)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS s.r.l., San Pietro al Natisone (UD), Italy.
- Breeder: Envigo RMS B.V., Kreuzelweg 53, 5961 NM Horst, Netherlands.
- Females nulliparous and non-pregnant: yes.
- Age: 6 to 8 weeks old.
- Weight range at arrival: 198.3 to 202.6 grams (males); 189.7 to 189.9 grams (females).
- Housing: clear polysulfone H-Temp solid bottomed cages (Tecniplast Gazzada S.a.r.l., Buguggiate, VA, Italy) measuring 59.5×38×20 cm during acclimatisation period and 42.5×26.6×18.5 cm during the study with nesting material provided into suitable bedding bags. At allocation animals were individually caged.
- Diet: ad libitum throughout the study, 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
- Water: ad libitum, drinking water supplied to each cage via a water bottle.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 2 °C.
- Humidity: 55 % ± 15 %.
- Air changes: approximately 15 to 20 air changes per hour.
- Photoperiod: artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Treatment area preparation: on the day before dosing (Day –1), a single area was clipped free of hair (by an electric clipper equipped with a suitable blade) on the dorsal surfaces of the trunk of each animal (approximately 10 % of body surface). Care was taken to avoid damage to the skin.
- Area of exposure: dorsal surfaces of the trunk of each animal (approximately 10 % of body surface).
- Type of wrap if used: a patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE: after exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarmwater.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Cage control: daily inspected and changed as necessary (at least 3 times/week)
- Mortality and morbidity observations: throughout the study, all animals were checked twice daily.
- Clinical signs: the animals were observed on the day of dosing; session 1: on dosing- session 2: approximately 1 hour after dosing- session 3: approximately 2 hours after dosing- session 4: approximately 4 hours after dosing and daily thereafter for a total of 14 days.
- Body weighing: all animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 8 and 15. Body weight change calculated for Days 8 and 15 of the dosing phase was relevant to Day 1 of the phase.
- Termination: all animals were sacrificed on Day 15 by carbon dioxide narcosis.
- Necropsy of survivors performed: yes. Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in male or female animals after treatment during the observation period.
Clinical signs:
No clinical signs were observed in male or female animals after treatment during the observation period.
Body weight:
Body weights and body weight changes were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
No abnormalities were found at necropsy examination performed on all animals at termination of the study

Applicant's summary and conclusion

Interpretation of results:
other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008
Conclusions:
LD50 > 2000 mg/kg
Executive summary:

The acute toxicity of the test material was investigated following dermal administration of a single dose to the rat, according to the OECD Guideline 402. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours, under semi-occlusive dressing. Animals were observed for mortality and clinical signs and were weighed on the day of allocation, on the day of dosing and on days 8 and 15. After 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No significant abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

LD50 > 2000 mg/kg