Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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))
GLP compliance:
yes (incl. certificate)
Remarks:
TNO Triskelion, Utrechtseweg 48, 3704 HE Zeist, The Netherlands
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Celitement
- Chemical name: Calcium hydrosilicate
- Physical state: White powder
- pH-value: 10.5
- Expiration date of the lot/batch: 12/2015
- Stability under test conditions: Hydration reaction with water
- Storage condition of test material: Room temperature protected from light, in original container in evacuated desiccator

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, the Netherlands
- Age at study initiation: at least 8 weeks old
- Weight at study initiation: mean body weight males 257 gram and females 191 gram
- Housing: macrolon cages (Type IV) with wood shavings (Lignocel) as bedding material and strips of paper (Enviro-dri) and a woodblock as environmental enrichment; individual housing during dermal exposure.
- Diet: standard laboratory diet (SDS Special Diets services, Whitham, England)
- Water: tap water (N.V.Vitens) ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45 - 65%
- Air changes (per hr): ca 10
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: solution of methyl cellulose in water 1%
Details on dermal exposure:
TEST SITE
- Area of exposure: at least 4 x 5 cm, i.e. an exposure area of at least 20 cm².
- % coverage: ca 10% of the total body surface.
- Type of wrap if used: a (5x5 cm) gauze patch, which was fixed to the application site by means of adhesive tape and the entire trunk of the rat was
wrapped with a bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm water
- Time after start of exposure: circa 24 hours.

TEST MATERIAL
A 400 mg/mL test concentration was prepared in a 1% aqueous methyl cellulose solution (1% MC)
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of each animal was recorded just prior to dosing and on days 3, 7 and 14 of the study. Individual skin reactions were recorded on days 1, 3, 7, and 14 of the study. Observations of clinical signs were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout an observation period of 14 days.
- Necropsy of survivors performed: yes, examined for gross pathological changes.

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 observed
Clinical signs:
No clinical signs were observed during the 14-day observation period.
Body weight:
All animals gained weight during the 14-day study.
Gross pathology:
Examination at necropsy of the animals did not reveal treatment-related gross alterations.
Other findings:
Upon removal of the patch, it appeared that on some areas the test material had adhered to the skin. Complete removal could not be done without damaging the skin underneath. Therefore, it was decided not to remove all of the test material, but to let the animal remove the remaining test material by cleaning (grooming). However, especially in females, (mechanical) damage to the skin could not be avoided and the resulting skin effects in the males and females were considered mostly due to the removal procedure. One day after removal of the patch, no signs of skin irritation were observed. On day 3 of the study, the skin effects generally consisted of very slight or well defined erythema, very slight or slight oedema and slight or moderate incrustation. On day 7 of the study, the severity of the skin effects had decreased considerably, especially in the males. On day 14 of the study, no signs of skin irritation were observed, but three females showed scar tissue (one in combination with very slight incrustation). The scar tissue was considered to be a result of the (mechanical damage) caused by the removal procedure.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions (OECD 402, GLP) the dermal LD50 of the test substance is considered to be higher than 2000 mg/kg body weight.
Executive summary:

In accordance with the OECD Guideline no. 402 and GLP the acute dermal toxicity of the test substance was examined in Wistar rats. Five rats per sex were exposed to 2000 mg/kg bw test substance for 24 hours under semi-occlusive conditions. After 24 hours the treated skin was washed with lukewarm water and animals were observed for 14 days after exposure. All animals gained weight during the 14 -day study. No mortality or clinical signs were observed after treatment. Dermal effects observed generally consisted of very slight or well-defined erythema, very slight or slight oedema and slight or moderate incrustation. Macroscopic examination of the surviving animals at the end of the observation period did not reveal any test article-related gross changes. The dermal LD50 of the test substance is considered to be higher than 2000 mg/kg body weight.