Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute oral toxicity (somewhat similar to OECD TG 401): LD50 = 2100 mg/kg bw.

Acute dermal toxicity (somewhat equivalent to OECD TG 402): No correct LD50 could be derived, the LD50 is very likely between 794 mg/kg bw and 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:
January 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Reliability has been presented as 2 because a protocol somewhat similar to OECD Guideline has been followed but pre-GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 210-225 g; females: 210-245 g
- Fasting period before study: not indicated

IN-LIFE DATES: not specified, all animals were sacrificed at the end of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE APPLIED: 2510 mg/kg bw
Doses:
1260, 1580, 2000 and 2510 mg/kg bodyweight
No. of animals per sex per dose:
1260 mg/kg bw: 3 males, 2 females
1580 mg/kg bw: 2 males, 3 females
2000 mg/kg bw: 3 males, 2 females
2510 mg/kg bw: 2 males, 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 100 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 950 - <= 2 260
Mortality:
At the lowest dose, no animal died while at the highest dose all animals (2 males and 3 females) died. At 1580 mg/kg bw, out of the two males and the three females tested, one male died. At 2000 mg/kg bw, from the three males and the two females tested, two males died. Mortality occured in one to six days, mostly within one day.
Clinical signs:
Reduced appetite and activity (one to three days in survivors), increasing weakness, ocular discharge and collapsing occured.
Gross pathology:
The animals who died during the study showed lung hyperemia, discoloration in areas of the liver and gastrointestinal inflammation. The animals who survived during the study showed normal viscera.
Other findings:
Male animals seemed to be more sensitive since 1 out of 2 and 2 out of 3 male animals tested, died at dose levels of 1580 and 2000 mg/kg bw, respectively, while no female animals died at these doses. Due to limited animal numbers it is justified to add the results of males and females per dose, resulting in an LD50 of 2100 mg/kg bw.
Interpretation of results:
other: Not classified, criteria not met
Remarks:
according to Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
In the acute oral toxicity test the substance showed an LD50 of 2100 mg/kg bw for male and female animals combined.
Executive summary:

An acute oral toxicity study was performed somewhat similar to OECD TG 401. Five rats per group (2 or 3 males and 2 or 3 females) were exposed to the substance in dose levels of 1260, 1580, 2000 and 2510 mg/kg bodyweight and observed for 14 days. At the lowest concentration no animal died, while at the highest concentration all animals died. Male animals seemed to be more sensitive since 1 out of 2 and 2 out of 3 male animals tested, died at dose levels of 1580 and 2000 mg/kg bw, respectively, while no female animals died at these doses. Mortality was observed in one to six days, mostly within one day. Clinical signs included reduced apetite and activity (one to three days in survivors), increasing weakness, ocular discharge and collapsing. At the end of the study, necropsy was performed on the surviving animals which showed normal viscera. Necropsy on animals that died during the study showed lung hyperemia, discoloration in areas of the liver and gastrointestinal inflammation. Due to the limited animal numbers it is justified to add results of males and females per dose, resulting in an LD50 of 2100 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
January 1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Results difficult to assess due to methodological deficiencies.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 1 or 2 animals per dosing level were used (instead of 5)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 1.8 - 2.1 kg; females: 1.8 - 1.9 kg

- No information on environmental conditions were provided.

IN-LIFE DATES: not indicated
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
794, 1000, 2000 and 3160 mg/kg bodyweight
No. of animals per sex per dose:
794 mg/kg bw: 1 female
1000 mg/kg bw: 1 male and 1 female
2000 mg/kg bw: 1 female
3160 mg/kg bw: 1 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 794 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Due to the limited number of animals tested, no correct LD50 can be derived.
Mortality:
794 mg/kg bw: only 1 female animal exposed, no death occurred;
1000 mg/kg bw: 2 animals (1 male and 1 female) were exposed from which 1 male animal died at day 6.
2000 mg/kg bw: only 1 female exposed which died at day 2.
3160 mg/kg bw: only 1 male exposed which died at day 1.
Clinical signs:
Reduced appetite and activity (two to four days in survivors), increasing weakness and collapsing were observed.
Gross pathology:
In animals who died during the study lung, liver and kidney hyperemia, slightly enlarged gall bladder, darkened spleen and gastrointestinal inflammation were observed. In animals who were sacrificed after the 14 day observation period, viscera appeared normal.
Interpretation of results:
other: EU CLP classification: Acute Dermal Toxicity Category 4: Harmful in contact with skin.
Remarks:
Though no correct LD50 can be drived, dermal toxicity is observed pointing towards EU CLP classification.
Conclusions:
Due to the limited number of animals tested (only one or two per dose), no correct LD50 can be derived. However, despite the limitations of the study it can be seen that the acute dermal toxicity (LD50) of the substance is very likely between 794 and 2000 mg/kg bw.
Executive summary:

In this study performed somewhat equivalent to OECD TG 402 guideline, 5 rabbits (2 males and 3 females) were exposed to the substance. Only 1 or 2 animals per dose were used at dose levels of 794, 1000, 2000 and 3160 mg/kg bw. At the lowest dose, no mortality was seen, at 1000 mg/kg bw one out of two animals died (in six days), at the two highest dose levels both animals died (in two days and one day, resp.). Reduced appetite and activity (two to four days in survivors), increasing weakness and collapsing were observed. In animals that died during the study lung, liver and kidney hyperemia, slightly enlarged gall bladder, darkened spleen and gastrointestinal inflammation were observed. Animals, which were sacrificed after the 14 day observation period, the viscera appeared normal. Due to the limited number of animals tested, no correct LD50 can be derived. However, despite the limitiations in study design it can be seen that the LD50 is very likely between 794 and 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The acute dermal toxicity result is of limited quality but sufficient for this dossier.

Additional information

Acute oral toxicity

An acute oral toxicity study was performed somewhat similar to OECD TG 401. Five rats per group (2 or 3 males and 2 or 3 females) were exposed to the substance in dose levels of 1260, 1580, 2000 and 2510 mg/kg bodyweight and observed for 14 days. At the lowest concentration no animal died, while at the highest concentration all animals died. Male animals seemed to be more sensitive since 1 out of 2 and 2 out of 3 male animals tested, died at dose levels of 1580 and 2000 mg/kg bw, respectively, while no female animals died at these doses. Mortality was observed in one to six days, mostly within one day. Clinical signs included reduced apetite and activity (one to three days in survivors), increasing weakness, ocular discharge and collapsing. At the end of the study, necropsy was performed on the surviving animals which showed normal viscera. Necropsy on animals that died during the study showed lung hyperemia, discoloration in areas of the liver and gastrointestinal inflammation. Due to the limited animal numbers it is justified to add results of males and females per dose, resulting in an LD50 of 2100 mg/kg bw.

Acute dermal toxicity

In this study performed somewhat equivalent to OECD TG 402 guideline, 5 rabbits (2 males and 3 females) were exposed to the substance. Only 1 or 2 animals per dose were used at dose levels of 794, 1000, 2000 and 3160 mg/kg bw. At the lowest dose, no mortality was seen, at 1000 mg/kg bw one out of two animals died (in six days), at the two highest dose levels both animals died (in two days and one day, resp.). Reduced appetite and activity (two to four days in survivors), increasing weakness and collapsing were observed. In animals that died during the study lung, liver and kidney hyperemia, slightly enlarged gall bladder, darkened spleen and gastrointestinal inflammation were observed. Animals, which were sacrificed after the 14 day observation period, the viscera appeared normal. Due to the limited number of animals tested, no correct LD50 can be derived. However, despite the limitiations in study design it can be seen that the LD50 is very likely between 794 and 2000 mg/kg bw.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, the substance does not need to be classified for acute oral toxicity according to EU CLP (EC 1272/2008 and its amendments). However, according to GHS the substance would need to be classified into acute oral toxicity Category 5, H303: May be harmful if swallowed.

Though no correct dermal LD50 could be derived, based on the results of the acute dermal toxicity study, the substance is classified into Acute Dermal Toxicity Category 4 of EU CLP (EC 1272/2008 and its amendments) and GHS, H312: Harmful in contact with skin.