Registration Dossier

Administrative data

Description of key information

Oral: LD50 = > 2000 mg/kg bw, male/female rat, OECD 401, EU Method B.1, Manciaux 1998
Dermal: LD50 = > 2000 mg/kg bw, male/female rat, OECD 402, EU Method B.3, Pelcot 2002

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:
27 May 1998 to 10 June 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed in accordance with valid guidelines and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
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
- Age at study initiation: approximately 6 weeks
- Weight at study initiation (mean ± standard deviation): 186 ± 4 g (males); 139 ± 10 g (females)
- Fasting period before study: overnight (approximately 18 hours before dosing). Food was returned to cages 4 hours after dose administration.
- Housing: polycarbonate cages covered with a stainless steel lid. Each cage contained 4 - 7 animals of the same sex during acclimatisation period and 5 animals of the same sex during the treatment period.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 27 May 1998 to 10 June 1998
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(purified)
Details on oral exposure:
The test material was prepared in the vehicle at a concentration of 2000 mg/kg bw. It was administered to the animals under a volume of 10 mL/kg. The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 2 mL glass syringe. The volume administered to each animal was adjusted according to body weight determined on the day of treatment.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed frequently during the hours following administration and then at least once daily thereafter
- Frequency of weighing: bodyweight measurements were taken on the day of administration (day 1) and on days 8 and 15
- Necropsy of survivors performed: yes, by CO2 asphyxiation
- Other examinations performed: macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. In case of macroscopic lesions, organ samples were taken and preserved in 10 % buffered formalin.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the study.
Clinical signs:
No clinical signs were observed during the study.
Body weight:
The body weight gain of the animals was not influenced by treatment.
Gross pathology:
Macroscopic examination of the main organs of the animals killed at the end of the study revealed no apparent abnormalities.

Test animals

- Source: Iffa Crédo, 69210 L'Arbresle, France

- Diet: A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, none of the animals died and no clinical signs were recorded. The LD50 of the test material was therefore determined to be in excess of 2000 mg/kg bw. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute oral toxicity of the test material was determined in accordance with standardised guidelines EU Method B.1 and OECD 401. During the study rats received a sinlge oral dose of 2000 mg/kg under a volume of 10 mL/kg. The animals were checked for clinical signs, mortality and body weight gain for a period of 14 days following administration of the test material. A necropsy was performed on each animal at study termination. Under the conditions of the study, none of the animals died and no clinical signs were recorded. The LD50 of the test material was therefore determined to be in excess of 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed in accordance with valid guidelines and the study was conducted under GLP conditions. The study has been assigned a reliability score of 1 in accordance with the criteria of Klimisch (1997) and considered suitable as an accurate reflection of the test material.

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:
13 January 2000 to 27 January 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed in accordance with valid guidelines and the study was conducted under GLP conditions.
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
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
- Age at study initiation: approximately 8 weeks
- Weight at study initiation (mean ± standard deviation): 272 ± 8 g (males); 237 ± 10 g (females)
- Housing: animals of the same sex caged in groups of 1 - 7 during acclimitisation; animals were caged individually during treatment period
- Diet: animals had free access to food
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 13 January 2000 to 27 January 2000
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
(purified)
Details on dermal exposure:
TEST SITE
On the day before treatment, the dorsal area (6 cm x 8 cm) of each animal was clipped free of fur. A hydrophilic gauze pad was placed over the test material, covering an area representing approximately 10 % of the body surface area of the animals. The gauze pad was held in place by means of an adhesive hypoallergenic aerated semi-occlusive dressing and restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed with a moistened gauze pad.
- Time after start of exposure: 24 hours.

TEST MATERIAL
A single dose of 2000 mg/kg test material, moistened with 2 mL water, was applied to the test site.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
The dose applied to each animal was adjusted according to body weight determined on the day of treatment.

On the day of treatment, the test material was ground to a fine powder with a pestle and mortar.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed frequently during the hours following administration of the test material and at least once daily thereafter.
- Frequency of weighing: animals were weighed individually just before administration of the test material on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes, by CO2 asphyxiation
- Other examinations performed: a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen, and any other organs with obvious abnormalities) was performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the study.
Clinical signs:
No clinical signs were observed during the study.
Body weight:
The overall bodyweight gain of the treated animals was similar to that of historic control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
A yellow colouration of the skin due to the test material, which could have masked a well-defined erythema (grade 2) on days 2 and 3 in all the animals then a very slight erythema (grade 1) from days 4 to 6 in 15/10 animals (2 males and 3 females), was observed. When the colouration of the skin was no more present, no cutaneous reactions were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, none of the animals died and no clinical signs were recorded. The LD50 of the test material was subsequently determined to be in excess of 2000 mg/kg bw. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute dermal toxicity of the test material was determined in accordance with standardised guidelines OECD 402 and EU Method B.3. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. A yellow colouration of the skin due to the test material, which could have masked a well-defined erythema on days 2 and 3 in all the animals then a very slight erythema from days 4 to 6 in 15/10 animals, was observed. When the colouration of the skin was no more present, no cutaneous reactions were observed. The bodyweight gain of the animals was not influenced by treatment. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was subsequently estimated to be in excess of 2000 mg/kg to both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed in accordance with valid guidelines and the study was conducted under GLP conditions. The study has been assigned a reliability score of 1 in accordance with the criteria of Klimisch (1997) and considered suitable as an accurate reflection of the test material.

Additional information

Oral

The acute oral toxicity of the test material was determined in accordance with standardised guidelines EU Method B.1 and OECD 401. During the study, rats received a single oral dose of 2000 mg/kg under a volume of 10 mL/kg. The animals were checked for clinical signs, mortality and body weight gain for a period of 14 days following administration of the test material. A necropsy was performed on each animal at study termination. Under the conditions of the study, none of the animals died and no clinical signs were recorded. The LD50 of the test material was subsequently determined to be in excess of 2000 mg/kg bw.

Dermal

The acute dermal toxicity of the test material was determined in accordance with standardised guidelines OECD 402 and EU Method B.3. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. A yellow colouration of the skin due to the test material, which could have masked a well-defined erythema on days 2 and 3 in all the animals then a very slight erythema from days 4 to 6 in 15/10 animals, was observed. When the colouration of the skin was no longer present, no cutaneous reactions were observed. The bodyweight gain of the animals was not influenced by treatment. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was subsequently estimated to be in excess of 2000 mg/kg to both male and female rats.

Inhalation

In accordance with column 2 of section 8.5.2 of REACH, the acute toxicity by inhalation study has been omitted as scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use. The acute toxicity of the substance has been determined adequately by the oral and dermal routes.


Justification for selection of acute toxicity – oral endpoint
Only one study is available.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the test material does not require classification as no signs of toxicity were noted during the course of either study.