Registration Dossier

Administrative data

Description of key information

The substance is non-toxic when provided to rats at high dose-levels by oral and dermal routes, two routes for which absorption and metabolism profiles may be different. For these routes, the conclusion is “Not classified - based on specific, valid data on the substance”.
Toxicity upon inhalation of the substance was not investigated. The acute toxicity by inhalation should be limited because of the physico-chemical characteristics of the substance (more than 98% of the particles were between 2.8 and 4 mm). The conclusion is “Not classified - based on weight-of-evidence analysis”.
Data from other in vivo studies (sections 5.3, 5.5, 5.6 and 5.9) do not show evidence of any irreversible damage after single exposure (risk phase R68): the conclusion is “Not classified - based on specific, valid on the substance (oral and dermal routes)/based on weight-of-evidence analysis (inhalation, in the absence of assays”.

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:
1996-08-22 to 1996-09-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no autopsy at the end of the study but no death, normal clinical examination and weight evolution
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
absence of autopsy at the end of the study
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- 5 male rats and 5 non gestating rats about 200 to 250g at the time of the trial
- source of the animals: Janvier Le Genest St Isle 53940 FRANCE
- acclimation: at least 5 days in the animal shelter of the laboratory
- house: individual polystyrene cages, room temperature between 18 and 22°C, relative humidity between 50 and 80°C, filtered and recycled air at 3000 cubic meters/hour, 12/12 hours light/dark cycle.
- food (aliment extralabo M20 Ets Pietrement) and tap water ad libitum
Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
the single dose was administered with a syringue and the gastro-oesophageal probe.
Doses:
2 g/kg
No. of animals per sex per dose:
5 male rats
5 femal rats
Control animals:
no
Details on study design:
- 18 hours before D0: the animals were maintained on a hydric diet
- D0: the animals were weighed. Administration of the product at 2 g/kg bw. Observation of the animals at T+ 1/4h, T+1h, up to T+6h.
- D1 to D14: daily observation of the animals. Behavioural abnormalities (apathy, excitation, palpebral ptosis), nervous attacks (comas, trembling, convulsions), digestive effects (refusal of food or drink, modification of the volume or appearance of faeces or urina) toxic and corrosif vascular effects (buccal, anal, nasal bleeding), eventual deaths
- D7: weighting of the survivals
- D14: weighting of the survivals
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
absence of clinical side effects
Body weight:
normal weight evolution
Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The test substance has an innocuousness by oral route at a dose of 2 g/kg bw according to the protocol defined in the guideline.
Executive summary:

The test substance was administrated in 5 male and 5 female rats at the dose of 2 g/kg bw according to the guideline EEC 884L251 25/04/84.

Mortality, clinical behavioural and weight evolution were recored for 14 days after the single oral administration.

The absence of mortality or other clinical side effects (severe apathy, loss of weight) allows to conclude in the total innocuousness of the tested product at the dose administered. This allows to classify the product as non toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Conclusions:
Effects upon inhalation of the substance were not investigated. This is not required as acute toxic potential was investigated for two other routes (oral and dermal), the substance is non-volatile (vapour pressure of 6.66 x 10-5 Pa) and the granulometry of the substance (only 0.7% of particles are smaller than 1 mm as the substance is in the form of pellets or flakes) would lead to negligible exposure of terminal airways.
Executive summary:

Effects upon inhalation of the substance were not investigated. This is not required as acute toxic potential was investigated for two other routes (oral and dermal), the substance is non-volatile (vapour pressure of 6.66 x 10-5 Pa) and the granulometry of the substance (only 0.7% of particles are smaller than as the substance is in the form of pellets or flakes) would lead to negligible exposure of terminal airways.

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:
2007-11-27 to 2008-01-15
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals:
Twenty Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle– France), an acclimatisation period of at least five days was performed. At the beginning of the study, the animals of the treated group weighed between 228 g and 246 g (males) and between 198 g and
220 g (females) and were 7-8 weeks old.
Group 1 (control): 5 male rats and 5 female rats
Group 2 (treated): 5 male rats and 5 female rats
Housing:
During the treatment, the animals were kept in individual cage. At D3, the animals were put into their cage by 2 or 3. The rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry; the environmental conditions were:
- temperature : between 19 °C and 22 °C
- relative humidity : between 34 % and 52 %
- lighting time: 12 hours daily

- drinking water (tap water form public distribution system) and foofstuff were supplied freely. Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux).
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
-Animals from Group 2 received by topical application (10% of area body), under porous gauze dressing, an effective dose
of 2000 mg/kg body weight of th substance, diluted in distilled water under a volume of 10 mL/kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressings were removed and the treated areas were rinsed with distilled water.
Animals from Group 1 received in the same experimental conditions the control item (distilled water) under a volume of 2 mL/kg body weight.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw
- Concentration : 10ml/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24 hours exposure
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male rats
5 female rats
Control animals:
yes
Details on study design:
-D0: weighting of the animals. Topical application under porous gauze dressing of the test product for the treated group and of the vehicle (distilled water) for the control group.
- D1: removing of the gauze dressing and rinsing of the treated areas
- D2, D7 and D14: observation of the animals and weighing
- D14: the animals were anaesthetised and autopsy was performed on the organs likely to be modified in cases of acute toxicity.

- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight,organ weight, histopathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occured during the study
Clinical signs:
Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed.
Body weight:
The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.
Other findings:
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test substance is higher than 2000 mg/kg body weight by dermal route in the rat.
According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test substance needs not be classified. No symbol and risk phrase are required.
Executive summary:

The test substance was applied onto the intact skin of 10 Sprague Dawley rats (5 males and 5 females) at the single dose of 2000 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline. n° 402 dated February 24th, 1987 and the test method B.3 of the directive. n° 92/69/EEC.

No mortality occurred during the study.

Neither cutaneous reactions nor systemic clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50 of the test substance is higher than 2000 mg/kg body weight by dermal route in the rat.

According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test substance needs not be classified. No symbol and risk phrase are required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The substance is not classified for Acute toxicity according to GHS