Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 31 May to 24 November 2011
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

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:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1-phenyloctadecane-1,3-dione and phenylicosane-1,3-dione
EC Number:
915-316-2
Molecular formula:
C50H80O4
IUPAC Name:
Reaction mass of 1-phenyloctadecane-1,3-dione and phenylicosane-1,3-dione
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks
- Weight (mean) at study initiation: 361 g for males and 225 g for females
- Fasting period before study: No
- Housing: The animals were housed by five, from the same sex and group, in polycarbonate cages with stainless steel lids (Tecniplast 2000P, 2065 cm2, 61 cm x 43.5 cm x 21.5 cm). Autoclaved sawdust (SICSA, Alfortville, France) was placed in each cage. Cocoon was given as enrichment
- Diet (ad libitum): SSNIFF R/M-H pelleted diet, batch No. 9945009 (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water (filtered with a 0.22 µm filter)
- Acclimation period: 8 days for males and 5 days for females

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12h/12h (7:00 - 19:00)

IN-LIFE DATES: From: 31 May to 14 June 2011 for males and from 03 June to 17 June 2011 for females

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:


TEST SITE
- Area of exposure: back of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: The test item was placed on a gauze pad moistened with drinking water treated by reverse osmosis. The gauze pad was held in place with an aerated hypoallergic dressing for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done) :After removal of the dressing, any residual test item was removed using a dry cotton pad
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight (the quantity of test item applied to each animal was adjusted according to the body weight recorded on the day of dose application).
- Concentration (if solution): not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was observed after treatment as follows at least once during the first 30 minutes, periodically during the first 4 hours, then once a day, at approximately same time, for the recording of clinical signs. From day 2, any local reactions at the treatment site were also noted. The body weight of each animal was recorded the day of allocation of the animals into groups then on the day of treatment and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
Body weight:
No test item treatment-related effects were noted on body weight.
Gross pathology:
The few macroscopic findings noted at necropsy consisted of agenesis of the right kidney, testis and epididymis with compensatory enlargement of the left kidney in a single group 2 male (W24093). This developmental anomaly, occasionally recorded in the Sprague-Dawley rats, was unrelated to the test item administration.
Other findings:
Very slight erythema was noted in 2/5 females between days 2 and 6. Two other females showed well-defined erythema on days 2 and/or 3 followed by a very slight erythema between days 3 and 4 for one of them and between days 4 and 9 for the second one. For the fifth female, the erythema was moderate to severe between days 2 and 5. The intensity decrease to well-defined on day 6 and it was still noted on day 7. In addition, very slight to slight dryness was noted in 3/5 females between days 3 and 7. Scabs were also noted at the application site of 2/5 females between days 2 and 9.

Very slight erythema was noted on day 2 or 3 in 3/5 males and between days 2 and 4 in 2/5 males. In addition, scabs were noted at the application site for 2 males between days 5 and 6 and between days 3 and 5, respectively.

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 the current study, the test item showed no signs of toxicity in female and male rats over a period of 14 days when applied dermally once at 2000 mg/kg bw. The LD50 can therefore be concluded to be greater than 2000 mg/kg bw. Based on this result the reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).
Executive summary:

RHODIASTAB 55 Phas been tested in an acute dermal toxicity study usingSprague‑Dawley rats, according to OECD guideline n° 402 and EU guideline n° B.3 in compliance with Good Laboratory Practice.

The test item was applied once under semi-occlusive conditions to the clipped back of the animals at a dose level of 2000 mg/kg for 24 h (5 males + 5 females per dose, 10% of the total body surface).

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days after the single administration of Rhodiastab 55P. All animals were subjected to necropsy.

No mortality was recorded in both groups during the study. Body weight gain of the treated animals was not affected by treatment. Local reactions at the application sites consisted in erythema, scab and/or dryness observed in some animals during the first week of the observation period. Local reactions had totally reversed at the end of the observation period. At necropsy, no abnormalities were observed in any animal.

As the LD 50 is higher than 2000 mg/kg, the reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).

This acute dermal study is classified as acceptable. It satisfies the OECD 402 guideline requirements for an acute dermal study in the rat.