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Administrative data

Description of key information

Single exposure (acute) studies indicate that the substance is of low toxicity if swallowed (rat LD0 > or = 2000 mg/kg bw) or absorbed through skin (rat LD0> or = 2000 mg/kg bw).
No information regarding the acute inhalation toxicity of the substance is available.

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:
From 1999-12-31 to 2001-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Annex V (B1 tris)
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
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8 weeks
- Weight at study initiation: 249 to 279g for males, 207 to 222g for females
- Fasting period before study: overnight fasted
- Housing: group of 3 by sex and by cage in solid-floor polypropylene cages.
- Diet: ad libitum3 to 4 hours after dosing
- Water : ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark /12 hrs light

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.88 ml/kg. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing and taking into account that the specific gravity was 1.064

Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for death or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight and gross pathological examination.
Statistics:
none
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
Male: no mortalities
Female: no mortalities
Clinical signs:
- In males, there were no signs of systemic toxicity during the study period.
- In females, hunched posture was observed during the day of dosing and one day after in all animals. 1 female showed also noisy respiration, increased salivation and red/brown staining around the mouth.
Body weight:
All animals showed expected gains in bodyweight over the study period, except one female which showed expected gain during the first week and bodyweight loss during the second week of the study.
Gross pathology:
Abnormalities noted at necropsy of one male were enlarged right kidney and reduced left kidney. No other abnormalities were noted .
Other findings:
None

Table 7.2.1/1: signs of reaction to treatment

Clinical signs

No. of rats in groups of 3 showing signs

Dose (mg/kg b.w.)

2000

M

F

Hunched posture

0

3

Noisy respiration

0

1

Increased salivation

0

1

Staining around mouth

0

1

 

Table 7.2.1/2: Weekly Bodyweight changes

Dose level mg/kg b.w

Sex

Bodyweight Gain (g) during Week

1

2

2000

F

38

18

F

34

-22

F

17

60

M

58

55

M

56

56

M

61

31

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortalities were noted in rats treated by oral route with a single dose of 2000 mg/kg bodyweight.
Therefore, the substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.
Executive summary:

The substance was tested for acute oral toxicity according to OECD 423 guideline and in compliance with Good Laboratory Practices.

Groups of rats (3 /sex) were administered by gavage a single dose of the test substance at 2000 mg/kg b.w.. Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period. All surviving animals were necropsied at the end of the observation period.

No mortalities were observed throughout the study.

In males, there were no signs of systemic toxicity during the study period while hunched posture was observed in all females during the day of dosing and one day after. In addition, 1 female showed also noisy respiration, increased salivation and red/brown staining around the mouth.

Except this female which showed bodyweight loss during the second week of the study, the body weight gain was not affected in the remaining animals.

At necropsy, one male showed enlarged right kidney and reduced left kidney. No other abnormalities were noted.

The combined acute oral LD50 was found greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study

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:
From 2001-04-04 to 2001-04-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Annex V
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
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8 weeks
- Weight at study initiation: at least 200 g
- Fasting period before study: no
- Housing: individually in suspended polypropylene cages during the 24-hour exposure period and in group of 5 by sex for the remainder
of the study.
- Diet: ad libitum
- Water : ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark /12 hrs light

IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: approximately 10%
- Type of wrap :piece of surgical gauze placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied : 2000mg/kg bw undiluted
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for death or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight and gross pathological examination.
Statistics:
none
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
Male: no mortalities
Female: no mortalities
Clinical signs:
There were no signs of systemic toxicity during the study period.
Body weight:
The body weight gain was not affected by treatment with the test substance.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions (local):
-There were no signs of dermal irritation in males.
-Crust formation was noted at the treatment sites of 3 females 4 and 5 days after treatment. Hardened light brown-coloured scabs, which precluded evaluation of erythema and oedema, were noted in the 2 remaining females 4 to 14 days after dosing.

Table 7.2.1/1: Weekly Bodyweight changes

Dose level mg/kg b.w

Sex

Bodyweight Gain (g) during Week

1

2

2000

F

23

17

F

19

27

F

15

24

F

11

26

F

21

10

M

27

56

M

39

62

M

48

64

M

64

42

M

72

50

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortalities were noted in rats treated by dermal route with a single dose of 2000 mg/kg bodyweight.
Therefore, the substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.
Executive summary:

The dermal toxicity of the substance was tested in rats according to OECD 402 and EU B.3 guidelines. The test item was applied to the back of 5 male and 5 female Spragues-Dawley rats at a concentration of 2000 mg/kg bw. It was covered in gauze and allowed to be in contact with the skin for 24 hours. The animals were observed for 14 days and mortality, body weight, and clinical observations were recorded.

No mortality was observed during the study period. Animals showed expected gains in bodyweight over the study period. Following necropsy and macroscopic examination of internal organs, no abnormalities were detected.

There were no signs of dermal irritation in males. Skin reaction noted at the treatment sites of females included crust formation and hardened light brown-coloured scabs, which precluded evaluation of erythema and oedema.

The dermal LD0 in the study was equal or higher than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study

Additional information

Oral route:

In an acute oral toxicity study performed according to OECD 423 guideline and in compliance with Good Laboratory practices, groups of 3 male and 3 female rats received by gavage a single dose of 2000 mg/kg bw. Animals were then observed for 14 days following exposure. No mortalities were observed throughout the study. Hunched posture was observed in all females during the day of dosing and one day after. In addition, 1 female showed also noisy respiration, increased salivation and red/brown staining around the mouth. Except this female which showed bodyweight loss during the second week of the study, the body weight gain was not affected in the remaining animals. At necropsy, one male showed enlarged right kidney and reduced left kidney. The combined acute oral LD0 was found equal or greater than 2000 mg/kg bw.

Dermal route:

In an acute dermal toxicity study performed according to OECD 402 guideline and in compliance with Good Laboratory practices, groups of 5 male and 5 female rats were treated dermally with a single dose of 2000 mg/kg bw. Animals were then observed for 14 days following exposure. No mortalities were observed throughout the study.

Skin reaction were noted at the treatment sites of females included crust formation and hardened light brown-coloured scabs, which precluded evaluation of erythema and oedema. In all animals, autopsy findings were negative. The dermal LD0 was found equal or higher than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

Acute oral toxicity:

No mortalities were noted in rats treated by oral route with a single dose of 2000 mg/kg body weight. On the basis of this study and according to regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures, no classification is warranted with respect to acute oral toxicity.

Acute dermal toxicity:

No mortalities were noted in rats treated by dermal route with a single dose of 2000 mg/kg body weight. On the basis of this study and according to regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures, no classification is warranted with respect to acute dermal toxicity.