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Administrative data

Description of key information

Oral Toxicity: LD50 > 2000 mg/kg bw, OECD 401, EU Method B1, Jouffrey 1995.
Dermal Toxcicity: LD50 > 2000 mg/kg bw, OECD 402, EU Method B3, Jouffery 1996.

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 May 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, done to a valid guidelines and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
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: ~ 6 weeks old
- Weight at study initiation: Males 171 ± 8 g, females 135 ± 5 g.
- Fasting period before study: Overnight for approximately 18 hours prior to dosing, food was reinstated 3-4 hours after administration of the test material.
- Housing: 5 per sex per cage, in polycarbonate cages (48 x 27 x 20 cm) covered with a stainless steel lid.
- Diet (e.g. ad libitum): pelleted diet ad libitum.
- Water (e.g. ad libitum): filtered water ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hr light/dark cycle
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg, the dose volume was adjusted according to the body weight determined on the day of treatment.

DOSAGE PREPARATION: The test solution was prepared in the vehicle on the day of treatment.
Doses:
2000 mg/kg bw of active material (corrected for purity)
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
- Necropsy of survivors performed: yes
- Examinations and frequency of observations:
Clinical signs: Animals were observed frequently in the hours following administration, and then at least once daily thereafter for a period of 14 days. Any signs were recorded on an individual basis.
Mortality: Animals were checked frequently for mortality and signs of morbidity in the hours following administration and then twice daily thereafter.
Body weight: Animals were weight prior to administration and then on days 8 and 15.
Body weight gain of the treated animals was compared to a reference curve created at the test facility, of control animals with the same initial weight.
Necropsy: Animals were euthanized on day 15 and macroscopic examinations were performed.
Examination included; opening of the thoracic and abdominal cavities and examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any with signs of abnormalities).
No microscopic examinations were performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality was observed at 2000 mg/kg.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
No treatment related effects were observed on body weight gain.
Gross pathology:
Macroscopic examination revealed no abnormalities in the animals.

Table 1: Mean Body Weight and Mean Body Weight Gain (g)

Sex

Body Weight on Days

1

Gain

8

Gain

15

Male

171 (± 8)

80 (± 7)

252 (± 15)

64 (± 9)

316 (± 17)

Female

135 (± 5)

46 (± 16)

181 (± 15)

24 (± 4)

206 (±16)

(± Standard Deviation)

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, no signs of mortality or treatment related toxicity were observed in any of the animals exposed to the test material via oral gavage. Therefore the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.
Executive summary:

The acute oral toxicity of the test material was determined in a study conducted under GLP conditions in accordance with the standardised guidelines OECD 401 and EU method B.1, using the fixed dose procedure.

Five male and 5 female Sprague-Dawley rats were exposed to the test material at 2000 mg/kg bw via oral gavage. The test material was dosed at 10 mL/kg bw in distilled water.

Under the conditions of the test, no overt signs of toxicity or mortality were observed in any of the treated animals, and body weight gain was normal. Furthermore, macroscopic examinations at necropsy revealed no abnormalities. Based on these observations the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed under GLP conditions to standardised guidelines. The report is conclusive and reported to a sufficient standard for classification. In accordance with the principles for assessing data quality defined by Klimisch et al (1997), this study was assigned a reliability score of 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:
14 December 1995 to 28 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, done to a valid guidelines and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
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: ~ 8 weeks old
- Weight at study initiation: Males 296 ± 4 g, females 232 ± 7 g.
- Housing: Individually during treatment in polycarbonate cages (35.5 x 23.5 x 19.3 cm). During acclimatisation animals were housed in groups by sex in polycarbonate cages (48 x 27 x 20 cm).
- Diet (e.g. ad libitum): pelleted diet ad libitum.
- Water (e.g. ad libitum): filtered water ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hr light/dark cycle
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Site preparation: The hair was clipped on the day of dosing from an area 6 x 8 cm. Only animals with healthy intact skin were used.
- Area of exposure: 5 x 6 cm for females and 5 x 7 cm for males.
- % coverage: 10 % of the body surface of each animal was treated.
- Type of wrap if used: The test material was applied to a hydrophilic gauze pad, pre-moistened with 2 mL of distilled water. The gauze was held in place using an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material was removed with a gauze pad moistened with water.
- Time after start of exposure: 24 hours.
Duration of exposure:
24 hours
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
- Necropsy of survivors performed: yes
- Examinations and frequency of observations:
Clinical signs: Animals were observed frequently in the hours following administration, and then at least once daily thereafter for a period of 14 days. Type, time of onset and duration of clinical signs and local cutaneous reactions were recorded on an individual basis.
Mortality: Animals were checked frequently for mortality and signs of morbidity in the hours following administration and at least once daily thereafter. The time of death was recorded individually in terms of hours after treatment.
Body weight: Animals were weight prior to administration on day 1 and then on days 8 and 15.
Body weight gain of the treated animals was compared to a reference curve created at the test facility, of control animals with the same initial weight.
Necropsy: Animals were euthanized on day 15 and macroscopic examinations were performed.
Examination included; opening of the thoracic and abdominal cavities and examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any with signs of abnormalities).
In the case of macroscopic lesions, organ samples were taken and preserved in 10 % buffered formalin.
No microscopic examinations were performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs of toxicity were observed during the study.
Slight orange colouration of the test site was observed in all animals on day 2. Crusts were noted in two males and two females on day 3; they persisted up to day 5 in one male and one female.
Body weight:
A slight decrease in body weight gain was noted in females in the first week only. The body weight gain in males was not affected.
Gross pathology:
Macroscopic examination of the main organs revealed no apparent abnormalities.

Table 1: Mean Body Weight and Mean Body Weight Gain (g)

Sex

Body Weight on Days

1

Gain

8

Gain

15

Male

296 (± 4)

37 (± 11)

334 (± 15)

50 (± 5)

384 (± 18)

Female

232 (± 7)

4 (± 4)

235 (± 6)

10 (± 13)

245 (± 15)

(± Standard Deviation)

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, no signs of mortality or treatment related toxicity were observed in any of the animals exposed to the test material applied under a semi-occlusive dressing. Therefore the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.
Executive summary:

The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions in accordance with the standardised guidelines OECD 402 and EU method B.3.

Five male and 5 female Sprague-Dawley rats were exposed to the test material at 2000 mg/kg bw applied in its original form under a semi-occlusive dressing.

Under the conditions of the test, no overt signs of toxicity or mortality were observed in any of the treated animal. Body weight again was slightly decreased in females in the first week only, whereas male body weight gain was not affected. Macroscopic examinations at necropsy revealed no abnormalities.

Based on these observations the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed under GLP conditions to standardised guidelines. The report is conclusive and reported to a sufficient standard for classification. In accordance with the principles for assessing data quality defined by Klimisch et al (1997), this study was assigned a reliability score of 1.

Additional information

ORAL

The acute oral toxicity of the test material was determined in a key study by de Jouffrey (1995). The study was conducted under GLP conditions in accordance with the standardised guidelines OECD 401 and EU method B.1, using the fixed dose procedure.

Five male and 5 female Sprague-Dawley rats were exposed to the test material at 2000 mg/kg bw via oral gavage. The test material was dosed at 10 mL/kg bw in distilled water.

Under the conditions of the test, no overt signs of toxicity or mortality were observed in any of the treated animals, and body weight gain was normal. Furthermore, macroscopic examinations at necropsy revealed no abnormalities. Based on these observations the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.

DERMAL

The acute dermal toxicity of the test material was determined in a key study by de Jouffery (1996). The study was conducted under GLP conditions in accordance with the standardised guidelines OECD 402 and EU method B.3, using the fixed dose procedure.

Five male and 5 female Sprague-Dawley rats were exposed to the test material at 2000 mg/kg bw applied in its original form under a semi-occlusive dressing.

Under the conditions of the test, no overt signs of toxicity or mortality were observed in any of the treated animal. Body weight again was slightly decreased in females in the first week only, whereas male body weight gain was not affected. Macroscopic examinations at necropsy revealed no abnormalities.

Based on these observations the LD50 of the test material was determined to be > 2000 mg/kg bw in both male and female rats.


Justification for selection of acute toxicity – oral endpoint
This is the only available study that addresses acute oral toxicity of the test material.

Justification for selection of acute toxicity – dermal endpoint
This is the only available study that addresses acute dermal toxicity of the test material.

Justification for classification or non-classification

ORAL TOXICITY

In accordance with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute oral toxicity.

DERMAL TOXICITY

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute dermal toxicity.