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Description of key information

Oral LD50: between 300 - 500 mg/kg bw

Dermal LD50 > 2000 mg/kg bw

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:
July from 02nd to 11th, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted on 22th March, 1996
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
For the purpose of the 2000 mg/kg b.w. dose level the test material was used as supplied.
For the purpose of the 200 mg/kg b.w. dose level the test material was freshly prepared as required as a solution in arachidis oil.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: ca. 8 weeks old.
- Weight at study initiation: at least 200 g.
- Acclimation period: at least 5 days.
- Housing: in group of three by sex, in solid-floor polypropylene cages furnished with woodflakes.
- Identification: ink-marking on the tail.
- Fasting period before study: overnight before dosing.
- Diet: ad libitum, rat and mouse Expended Diet no. 1.
- Water: free access to drinking water.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Humidity: 30 - 70 %
- Air changes: at least 15 ACH
- Photoperiod: 12 hours dark

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
- Concentration: 20 mg/ml at dose level of 200 mg/kg bw
- Dose volume: 1.54 ml/kg at dose level of 2000 mg/kg bw; 10 ml/kg at dose level of 200 mg/kg bw
Doses:
2000 and 200 mg/kg bw
No. of animals per sex per dose:
3 females at 2000 mg/kg bw
3 females and 3 males at 200 mg/kg bw
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: animals were observed for death or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequent once daily for up to 14 days. Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment or at death.
- Necropsy of survivors performed: yes. all animals were subjected to gross necropsy. External examination and opening of the abdominal and thoracic cavities for examination of major organs were performed. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
300 - 500 mg/kg bw
Based on:
test mat.
Mortality:
All females treated at 2000 mg/kg bw and one female treated at the dose level of 200 mg/kg bw were found dead during the day of dosing.
Clinical signs:
other: Signs of systemic toxicity noted in animals treated at 2000 mg/kg bw were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, ptosis, tiptoe gait and coma. Hunched posture was noted in surviving females treated at a dose l
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were haemorrhagic and abnormally red lungs, dark liver, dark kidneys, haemorrhage and sloughing of the gastric mucosa, non-glandular region of the stomach and small and large intestines.

No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Mortality data

Dose level mg/kg b.w. Sex No. animals Deaths during day of dosing (hours) Deaths during day of dosing (days) Deaths
1/2 1 2 4 1 2 3 4 5 6 7 8 until 14
2000 F 3 1 0 1 1 - - - - - - - - 3/3
200 F 3 1* 0 0 0 0 0 0 0 0 0 0 0 1/3
M 3 0 0 0 0 0 0 0 0 0 0 0 0 0/3
Interpretation of results:
other: Acute Tox. 4 (H302), according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 in the range of 300 - 500 mg/kg bw
Executive summary:

The study was performed according to OECD 423 (1996). A group of three females were treated orally by gavage with the test material at a dose level of 2000 mg/kg bw and, subsequently, three females and three males were treated at 200 mg/kg bw

At the higher dose level 3/3 females were found dead; while at the lower dose level 5/6 animal survived (1 female dead). Based on the present results, the acute oral median LD50 was estimated to be in the range of 300 - 500 mg/kg bw.

Conclusion

LD50 is in the range of 300 - 500 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw

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:
June from 02nd to 11th, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 24th,02,1987
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: ca. 8 weeks.
- Weight at study initiation: at least 200 g.
- Fasting period before study: overnight before dosing.
- Housing: polypropylene cages.
- Diet: Rat and Mouse Expended Diet no. 1.
- Water: free access to tapwater.
- Acclimation period: at least 5 days.
- Identification: ink-marking on the tail.

ENVIRONMENTAL CONDITIONS
- Temperature:19 - 25 °C
- Humidity: 30 - 70 %
- Air changes: at least 15 ACH
- Photoperiod: 12 hours dark
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Coverage: 10 % of the total body surface area.

REMOVAL OF TEST SUBSTANCE
- Modality: treated skin wiped with cotton wool moistoned with distilled water.
- Time after start of exposure: after 24 hours the bandage was removed.

TEST MATERIAL
- Amount applied: 1.54 ml/kg


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males per 5 females
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Body weights
- Necropsy of survivors performed: yes

EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema...................................................0
Very slight erythema (barely perceptible)......1
Well-defined erythema....................................2
Moderate to severe erythema.........................3
Severe erythema to slight eschar formation...4

Oedema formation
No oedema..............................................................................................................0
Very slight oedema (barely perceptible).................................................................1
Slight oedema (edges well-defined)........................................................................2
Moderate oedema (raised ca. 1 mm).......................................................................3
Severe oedema (raised more than 1 mm; extending beyond area of exposure)....4
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
other: No signs of systemic toxicity.
Gross pathology:
No abnormalities noted.
Other findings:
No signs of dermal irritation in male animals.
Female animals showed light brown discoloration of the epidermis, small superficial scattered scabs and glossy skin.

Females individual dermal reactions

Dose level mg/kg b.w. Animal no. and sex Observation Effects noted after initiation of exposure (days)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
2000 1F Erythema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Other - Br Br Br Br Br Br BrSs BrSs SSG SSG SSG G G
2F Erythema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Other - Br Br Br Br Br Br BrSs BrSs SSG SSG SSG G G
3F Erythema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Other - Br Br Br Br Br Br BrSs BrSs SSG SSG SSG G G
4F Erythema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Other - Br Br Br Br Br Br BrSs BrSs SSG SSG SSG G G
5F Erythema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Oedema 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Other - Br Br Br Br Br Br BrSs BrSs SSG SSG SSG G G

Br = light brown discoloration of the epidermis; G = glossy skin; Ss = small superficial scattered scabs

Interpretation of results:
other: not classified, according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

The test was performed according to OECD 402 (1987).

A group of ten animals (5 males and 5 females) was given a single 24 -hour semi-occluded dermal application of undiluted test material at dose level of 2000 mg/kg b.w.

No deaths occurred. No signs of systemic toxicity and abnormalities at necropsy were noted.

Skin of male animals was not affected by the test material; light brown discoloration of the epidermis, small superficial scattered scabs and glossy skin were noted in females.

Conclusion

The acute dermal LD50 is higher than 2000 mg/kg bw

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

Additional information

ORAL ROUTE

The oral acute toxicity potential was tested according to OECD 423. A group of three females were treated orally by gavage with the test material at a dose level of 2000 mg/kg bw and, subsequently, three females and three males were treated at 200 mg/kg bw. All females treated at 2000 mg/kg bw and one female treated at the dose level of 200 mg/kg bw were found dead during the day of dosing. Signs of systemic toxicity noted in animals treated at 2000 mg/kg bw were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, ptosis, tiptoe gait and coma. Hunched posture was noted in surviving females treated at a dose level of 200 mg/kg with diarrhoea, noted in males and females treated at this dose level. Surviving animals appeared normal one or two days after dosing. Surviving animals showed expected gains in bodyweight over the study period. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic and abnormally red lungs, dark liver, dark kidneys, haemorrhage and sloughing of the gastric mucosa, non-glandular region of the stomach and small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

DERMAL ROUTE

The dermal acute toxicity was assayed, according to OECD 402. A group of ten animals (5 males and 5 females) was given a single 24 -hour semi-occluded dermal application of undiluted test material at dose level of 2000 mg/kg b.w. No deaths occurred and no signs of systemic toxicity. All animals showed expected gains of bw. Necropsy did not revealed any abnormalities noted. No signs of dermal irritation in male animals. Female animals showed light brown discoloration of the epidermis, small superficial scattered scabs and glossy skin.

Justification for classification or non-classification

The oral LD50 of the substance was determined to be in the range of 300 - 500 mg/kg b.w. Therefore, according to the Regulation EC 1272/2008 (CLP) it meets the criteria for classification as Acute Tox., category 4 (H302).

The dermal LD50 of the substance was determided to be higher than 2000 mg/kg b.w., therefore it does not meet the criteria for classification under the Regulation EC 1272/2008 (CLP).