Registration Dossier

Administrative data

Description of key information

Oral: LD50 = > 2000 mg/kg bw, male/female rat, OECD 401, EU Method B.1, de Jouffrey 1995a
Dermal: LD50 = > 2000 mg/kg bw, male/female rat, OECD 402, EU Method B.3, de Jouffrey 1996a

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:
14 June 1995 to 28 June 1995
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 to valid guidelines and the study was conducted under GLP conditions.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Stain: Sprague-Dawley ICO: OFA-SD (IOPS Caw)
- Age at study initiation: approximately 6 weeks
- Weight at study initiation (mean ± standard deviation): 176 ± 4 g (males); 146 ± 5 g (females)
- Fasting period before study: yes, 18 hours prior to dosing. Diet was returned 4 hours after administration of the test material.
- 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: pelleted dietm, ad libitum
- Water: filtered drinking water (0.22 µm), 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 14 June 1995 to 28 June 1995
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled)
Details on oral exposure:
The test material was prepared in the vehicle at the maximum concentration of 100 mg/mL and administered under a volume of 2 x 11 mL/kg in order to obtain a dose of 2200 mg/kg in finished product (test material) and 2000 mg/kg in active ingredient. The volume administered to each animal was adjusted according to bodyweight determined on the day of treatment.
Doses:
2200 mg/kg finished product (test material) = 2000 mg/kg active ingredient
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 twice daily (mortality) and at least once daily (clinical signs)
- 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
- 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.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
None of the animals died during the study.
Clinical signs:
No clinical signs were observed during the study. Pink colouration of the bedding was noted from days 4 to 8 in all animals.
Body weight:
Body weight gain of the animals was not affected by treatment.
Gross pathology:
Macroscopic examination of the main organs of the animals killed at the end of the study revealed no apparent abnormalities.
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 oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 401 and EU Method B.1. Rats received two oral doses 1100 mg/kg under a volume of 11 mL/kg, each. 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
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 to valid guidelines and the study was conducted under GLP conditions. As such, the study was assigned a reliability score of 1 according to 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:
7 December 1995 to 21 December 1995
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 to valid guidelines and the study was conducted under GLP conditions.
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Sprague-Dawley ICO: OFA-SD (IOPS Caw)
- Age at study initiation: approximately 8 weeks
- Weight at study initiation (mean ± standard deviation): 287 ± 4 g (males); 230 ± 5 g (females)
- Housing: Animals of the same sex caged in groups of 4 - 7 in polycarbonate cages (48 cm x 27 cm x 20 cm) during acclimatisation; animals were caged individually (35.5 cm x 23.5 cm x 19.3 cm) during treatment period.
- Diet: pelleted diet, ad libitum
- Water: Filtered drinking water (0.22 µm), 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 7 December 1995 to 21 December 1995
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
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 single dose of 2000 mg/kg of the test material, moistened with 2 mL water, was applied to the test site on a hydrophilic gauze pad. The gauze covered 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
Any residual test material was removed with a moistened (distilled water) gauze pad.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
The volume applied to each animal was adjusted according to body weight determined on the day of treatment.
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
- 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 and no cutaneous reactions were observed during the study.
Very slight to moderate red colouration of the test site was noted in all animals up to day 5.
Body weight:
The body weight gain of the animals were not influenced by treatment.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
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. Very slight to moderate red colouration of the test site was noted in all animals up to day 5. The body weight 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:
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 to valid guidelines and the study was conducted under GLP conditions. As such, the study was assigned a reliability score of 1 according to 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 the standardised guidelines OECD 401 and EU Method B.1. Rats received two oral doses 1100 mg/kg under a volume of 11 mL/kg, each. 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. Very slight to moderate red colouration of the test site was noted in all animals up to day 5. The body weight 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.

Both studies presented to assess the acute toxicity of the test material were performed in line with GLP and accepted standardised guidelines with a high standard of reporting. Both studies were assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material.

The available data are considered to be complete and the conclusion for both acute oral and acute dermal toxicity, LD50 > 2000 mg/kg, was taken forward for risk assessment.


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 1272/2008, the test material does not require classification for acute oral and acute dermal toxicity as no signs of toxicity were noted during the course of either study.