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Administrative data

Description of key information

The acute oral LD50 of the test material in the Sprague-Dawley rat was >2000 mg/kg body weight (OECD 401).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
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: Charles River Laboratories Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: 118 ± 3.1 g (males) and 94.9 ± 2.6 g (females)
- Fasting period before study: overnight
- Housing: Six to 10 animals were housed per cage (suspended metallic cages for rats) and reared on rat cage racks with automatic water supply syste.
- Diet: pellet food for rats MF (Oriental Yeast Co., Ltd.), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 55 ± 6
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.25, 0.5, 2, 5 and 20 (w/v)%

MAXIMUM DOSE VOLUME APPLIED: 1.0 mL/100 g
Doses:
25, 50, 200, 500 and 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: General signs and symptoms: every day. Animals were weighed on Day 0 (day of administration), immediately before administration, and on Days 2, 7 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No male or female from any of the five groups died during the study period.
Clinical signs:
In the 25, 50, 200 and 500 mg/kg groups, no male showed any abnormality, while in the 2,000 mg/kg group, body drooping began to be seen about 20 min after administration. All six males in this group showed this change thereafter together with sedation. In addition, several males also showed staggering, lacrimation, and collapse. A recovery was noted in 3 males the day after treatment, but sedation persisted in the other 3 with 2 having something red adhered to the nose. Three males showed decreases in spontaneous locomotion even on Day 2, but a recovery was seen on Day 3, and no abnormality was seen thereafter. In the 25, 50, 200 and 500 mg/kg groups, females also showed no abnormality, while in the 2,000 mg/kg group, body drooping began to be seen about 20 min after administration and all six females in this group showed this change and sedation thereafter with some also showing staggering, collapse and slowing of breathing. However, all six females showed a recovery the day after administration. No abnormality was seen thereafter.
Body weight:
In the 25, 50, 200 and 500 mg/kg groups, males showed changes in body weight similar to those seen in the control group (given only olive oil). In the 2,000 mg/kg group, weight gain was suppressed on Day 2, but a normal increasing tendency was observed thereafter with no difference compared to the control group. In the 25, 50, 200 and 500 mg/kg groups, females also showed changes similar to those seen in the control group. In the 2,000 mg/kg group, weight gain was suppressed on Day 2, but a normal increasing tendency was observed thereafter with no difference compared to the control group.
Gross pathology:
Necropsy conducted at the end of the study period in all surviving males and females from the 25, 50, 200, 500 and 2,000 mg/kg groups revealed no abnormality.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was estimated to be >2000 mg/kg bw in both males and females.
Executive summary:

In an acute oral toxicity study, performed according to OECD guideline 401, groups of 6 fasted Sprague-Dawley CD rats per sex per dose were treated once with the test substance at 0, 25, 50, 200, 500 and 2000 mg/kg dissolved in olive oil by oral gavage followed by a 14 -day observation period.All animals survived. In the 25, 50, 200 and 500 mg/kg groups, no abnormalities were observed. Signs of systemic toxicity noted during the study in the 2000 mg/kg bw dose group included body drooping, sedation, staggering, lacrimation, collapse, decrease in spontaneous locomotion, and slowing of breathing. Animals were without symptoms within 3 days. All animals showed expected gains in bodyweight over the study period, and no abnormalities were noted at necropsy. In conclusion, the acute oral LD50 of the test substance in Sprague-Dawley rat was estimated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
OECD guideline study, klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study, performed according to OECD guideline 401, groups of 6 fasted Sprague-Dawley CD rats per sex per dose were treated once with the test substance at 0, 25, 50, 200, 500 and 2000 mg/kg dissolved in olive oil by oral gavage followed by a 14 -day observation period. All animals survived. In the 25, 50, 200 and 500 mg/kg groups, no abnormalities were observed. Signs of systemic toxicity noted during the study in the 2000 mg/kg bw dose group included body drooping, sedation, staggering, lacrimation, collapse, decrease in spontaneous locomotion, and slowing of breathing. Animals were without symptoms within 3 days. All animals showed expected gains in bodyweight over the study period, and no abnormalities were noted at necropsy. In conclusion, the acute oral LD50 of the test substance in Sprague-Dawley rat was estimated to be greater than 2000 mg/kg bodyweight.


Justification for selection of acute toxicity – oral endpoint
Only study available, OECD guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Justification for classification or non-classification

Based on the findings of the oral acute toxicity study, classification for acute oral toxicity is not warranted according to Directive 67/548/EEC and according toEU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.