Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 401 in rats; rel.1)

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 July 11 to 25, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Stability under test conditions: Test substance is expected to be stable for the duration of testing
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Males: 179-202 g, females: 157-176 g
- Fasting period before study: Animals were fasted for approximately 18 h by removing feed from their cages. Feed was replaced approximately 3.5 h after dosing.
- Housing: Animals were singly housed in suspended stainless steel caging with mesh floors.
- Diet: Purina Rodent Chow #5012, ad libitum
- Water: Filtered tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-24 °C
- Humidity: 40-54 %
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From July 11 to 25, 2000
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
None
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for mortality, signs of gross toxicity, and behavioral changes at 1 and 3 h post-dosing and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.
- Frequency of weighing: Individual bodyweights of the animals were recorded shortly before test substance administration (initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: Yes; all rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No signs of gross toxicity, adverse pharmacologic effects or abnormal behavior were observed.
Body weight:
Surviving animals showed expected gains in bodyweight over the 14-day study period.
Gross pathology:
No gross abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 for the test substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline No. 401 and in compliance with GLP, group (5/sex/dose) of Sprague-Dawley rats were given a single oral (gavage) dose of test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or clinical signs were observed. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Oral LD50 Combined > 2000 mg/kg bw.

 

Under the test conditions, the test material is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
One GLP study conducted in compliance with OECD Guideline No. 401 without any deviation.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Additional information

Acute toxicity: oral

A key study was identified (Product Safety Labs, 2000). In this acute oral toxicity study, performed according to OECD Guideline No. 401 and in compliance with GLP, rats were given a single oral (gavage) dose of test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or clinical signs were observed. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

This study gave an oral LD50 combined (rats) > 2000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

Acute toxicity via Dermal route:

No data was available. Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity (Inhalation):

No data was available. Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available. Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Inhalation):

No data was available. Not required for substances at the REACH Annex VII tonnage level.