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Description of key information

The LD50 in rat following acute oral and dermal exposure were >5000 mg/kg bw and >2000 mg/kg bw , respectively.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
(no data on starting date) 25-NOV 1996 (date of report)
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: six weeks old
- Weight at study initiation: 188 +- 2 g for males and 150 +- 5 g for females.
- Fasting period before study: overnight period of approximately 18 hours prior to dosing
- Housing: five rats of the same sex were housed in polycarbonate cages
- Food consumption: A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France) ad libitum.
- Water consumption: filtered water by a Millipore membrane (0.22 µm), ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS:
- Temperature: 21 +- 2°C
- Humidity: 30 to 70 %
- Air changes: 12 cycles/hour of filtered, non recycled air
- Photoperiod: 12-hour light/dark cycle

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Vehicle:
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

- Maximum dose volume: 10 mL/kg
Doses:
5000 mg/kg b.w.
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:
> mortality and clinical signs: observed frequently during the hours after dosing.
Thereafter, observation at least once a day up to the end of the 14-day observation period. (day 15)
> body weights: determined prior to dosing (day 1), on days 8 and 15.
Body weight gain of the treated animals was compared to that of C.I.T. control animals with the same initial body weight.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred in males and females
Clinical signs:
The general behaviour of animals was not affected
Body weight:
No effect was observed, all surviving animals had gained weight
Gross pathology:
Macroscopic examination of the main organs showed no apparent abnormalities

Table 7.2.1/2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

5000

0

0

-

-

0

0

-

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 given orally once at 5000 mg/kg bw. The LD50 can therefore be concluded to be greater than 5000 mg/kg bw. The reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified for acute oral toxicity according to the criteria of Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).



Executive summary:

RHODIASTAB X5 was tested for acute oral toxicity in Sprague-Dawley rats in a limit dose assay.
The test substance, a powder, was administered diluted in corn oil. Animals were fastened overnight prior to treatment. The assay was conducted on a group of 10 rats (5 males, 5 females) with a dose of 5000 mg/kg b.w. administered by gavage in a single oral dose (maximum dose volume of 10 mL/kg b.w).
Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period. All surviving animals were necropsied at the end of the observation period.

No deaths occurred and no clinical signs were observed during the study. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

As the acute oral LD50 was found to be greater than 5000 mg/kg b.w. under the conditions of the test, 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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
GLP-compliant study performed according to OECD 401 guideline (Klimish score = 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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)
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
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
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).
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP-compliant study performed according to OECD 402 guideline (Klimish score = 1).

Additional information

Oral route:

Four studies, two of reliability 1 (rat studies ; de Jouffrey 1996 and Clouzeau 1994) and two of reliability 2 (one rat and one mouse studies ; Pasquet, 1978) according to Klimisch cotation criteria, are available for oral route. The 1996 study was selected as the key study since the tested dose (5000 mg/kg) in rat was higher than that tested in the other reliability 1 study (2000 mg/kg bw). The 1994 and 1978 studies were selected as supporting studies. No death occurred during the 2 -week observation period in either study. The LD50 for oral route in rats was higher than 5000 mg/kg. No classification for acute oral toxicity is therefore warranted on the basis on these in vivo data.

 

Dermal route:

One study of reliability 1 according to Klimisch cotation critera, is available for dermal route (Rokh, 2011). In this study 5 males and 5 females rats received a single topical application of the test substance at a dose level of 2000 mg/kg bodyweight. All animals were killed and examined macroscopically at the end of the observation period (day 15). There were no deaths and no systemic response to treatment in any animal throughout the study. Erythema, scab and/or dryness were observed in some animals during the first week of the observation period. Local reactions had totally reversed at the end of the observation period.

Based on this study, the LD50 for dermal route in rats was higher than 2000 mg/kg bw. No classification for acute dermal toxicity is therefore warranted on the basis on these in vivo data.

Acute inhalation toxicity was not assessed because the exposure to particles of an inhalable size is not anticipated with the uses of the substance owing to its low dustiness (assessed by visual observation) and fugacity (the vapour pressure of the substance being negligible (0.000018 Pa at 25 °C)). Moreover, systemic effects by the inhalation route are unlikely since, according to the granulometry study, the percentage of particles belonging to the respirable fraction (< 10 µm) is below 1%.


Justification for selection of acute toxicity – oral endpoint
Study performed according to OECD 401 guideline which showed the highest dose level tested with no mortality.

Justification for selection of acute toxicity – dermal endpoint
only one study available (GLP and OECD guideline 402 compliant).

Justification for classification or non-classification

As the acute lethal oral and dermal dose to rats of the reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane was demonstrated to be greater than 5000 and 2000 mg/kg bodyweight, respectively, the test substance does not have to be classified for acute toxicity according to according to the criteria of Directive 67/548/EEC (DSD) or Regulation (EC) No. 1272/2008 (CLP).