Registration Dossier

Administrative data

Description of key information

In an acute oral toxicity study with rats, performed equivalent to OECD 401 guidelines, an LD50 of >6800 mg/kg bw was determined.

In an acute dermal toxicity study with rats, performed equivalent to OECD 402 guidelines, an LD50 of >2000 mg/kg bw was determined.

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:
April 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Deviations: no details on test material, limited details on test animals and environmental conditions.
GLP compliance:
no
Remarks:
not present at the time of performance.
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: Young albino rats
- Weight at study initiation: 150 - 208 g
- Fasting period before study: 16 hours
- Housing: The animals were housed in stock cages. Following administration of the test substance, the rats were individually housed in suspended, wire-mesh cages.
- Diet: Free access to standard laboratory rat diet
- Water: Free access to water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
No data.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All doses were administered directly into the stomachs of the rats using a hypodermic syringe equipped with a ball-tipped intubating needle.
Doses:
4.6, 6.8, 10.2 and 15.4 g/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Initial and final body weights as well as all mortalities and/or reactions displayed were recorded.
- Necropsy of survivors performed: A necropsy was conducted on any animal which died during the study as well as on all surviving animals sacrificed at the end of the 14 days.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 800 mg/kg bw
Based on:
test mat.
Mortality:
All animals died at the dose levels of 10200 (within 2 days after dosing) and 15400 mg/kg bw (within 1 day after dosing) and all animals survived at the dose levels of 4600 and 6800 mg/kg bw.
Clinical signs:
Hypoactivity, ruffed fur and muscular weakness was observed among all animals (starting after dosing, and disappearing after max. 4 days). At the dose levels 6800, 10200 and 15400 mg/kg also lacrimation was observed and at the dose levels 10200 and 15400 mg/kg also prostration was observed.
Body weight:
All surviving animals showed a normal body weight increase.
Gross pathology:
Necropsy of the animals that died revealed hemorrhages in the gastrointestinal tracts. No gross pathologic alterations were noted among the animals sacrificed at the end of the 14-day observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study with rats, performed equivalent to OECD 401 guidelines, an LD50 of >6800 mg/kg bw was determined.
Executive summary:

The test item was tested in an acute oral toxicity study with rats, performed equivalent to OECD 401 guideline.

All animals died at the dose levels of 10200 and 15400 mg/kg bw and all animals survived at the dose levels of 4600 and 6800 mg/kg bw. Hypoactivity, ruffed fur, muscular weakness, lacrimation and prostration was observed among the animals. All surviving animals showed a normal body weight increase. Necropsy of the animals that died revealed hemorrhages in the gastrointestinal tracts. No gross pathologic alterations were noted among the animals sacrificed at the end of the 14-day observation period. Based on the results, an LD50 of >6800 mg/kg bw was determined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Comparable to guideline study with acceptable restrictions

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:
April 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Deviations: no details on test material, limited details on test animals and environmental conditions.
GLP compliance:
no
Remarks:
not present at the time of performance.
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: New Zealand
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: Young adult rabbits
- Weight at study initiation: 2.5 - 3.1 kg
- Housing: Individually housed in hanging rabbit cages
- Diet: Free access to standard laboratory rabbit ration
- Water: Free access to water
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
No data.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
Twenty-four hours prior to the dermal applications, the backs of the rabbits were shaved free of hair with electric clippers. The shaved area on each animal constituted about 30% of the total body surface area. The animals were then returned to their cages to await testing on the following day. The 24-hour waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close-clipping procedure and also permitted healing of any microscopic abrasions possibly produced during the process.
On the testing day, four rabbits received skin applications of the respective test material. The exposure site was covered by wrapping the trunk of the animal with an impervious plastic sheeting which was securely taped in place. This plastic wrap insured intimate contact of epidermis and test substance. To further prevent oral ingestion of the test substance, each animal was fitted with a light-weight, flexible plastic collar which was worn throughout the observation period.

REMOVAL OF TEST SUBSTANCE
- Washing: No
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality, local skin reactions, behavioral abnormalities and initial and final body weights were recorded.
- Necropsy of survivors performed: A necropsy was conducted on all animals at the end of the observation period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
No untoward behavioral reactions were exhibited by any of the animals.
Body weight:
Body weights were not significantly increased, neither decreased.
Gross pathology:
No gross pathologic alterations were noted.
Other findings:
Pale red erythema and slight edema were noted after 24 hours. By seven days, dryness was evident. Dryness persisted to the end of the 14-day observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study with rats, performed equivalent to OECD 402 guidelines, an LD50 of >2000 mg/kg bw was determined.
Executive summary:

The test item was tested in an acute dermal toxicity study with rats, performed equivalent to OECD 402 guideline.

No deaths occurred. No untoward behavioral reactions were exhibited by any of the animals. Body weights were not significantly increased, neither decreased. No gross pathologic alterations were noted. Pale red erythema and slight edema were noted after 24 hours. By seven days, dryness was evident. Dryness persisted to the end of the 14-day observation period. Based on the results, an LD50 of >2000 mg/kg bw was determined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Comparable to guideline study with acceptable restrictions

Additional information

Acute toxicity: oral

The test item was tested in an acute oral toxicity study with rats, performed equivalent to OECD 401 guideline.

All animals died at the dose levels of 10200 and 15400 mg/kg bw and all animals survived at the dose levels of 4600 and 6800 mg/kg bw. Hypoactivity, ruffed fur, muscular weakness, lacrimation and prostration was observed among the animals. All surviving animals showed a normal body weight increase. Necropsy of the animals that died revealed hemorrhages in the gastrointestinal tracts. No gross pathologic alterations were noted among the animals sacrificed at the end of the 14-day observation period. Based on the results, an LD50 of >6800 mg/kg bw was determined.

Acute toxicity: dermal

The test item was tested in an acute dermal toxicity study with rats, performed equivalent to OECD 402 guideline.

No deaths occurred. No untoward behavioral reactions were exhibited by any of the animals. Body weights were not significantly increased, neither decreased. No gross pathologic alterations were noted. Pale red erythema and slight edema were noted after 24 hours. By seven days, dryness was evident. Dryness persisted to the end of the 14-day observation period. Based on the results, an LD50 of >2000 mg/kg bw was determined.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on this data, the substanceis considered not to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.