Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 - 25 Jul 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted on 17 December 2001
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, INC.
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8.5 to 9 weeks
- Fasting period before study: from the day prior to administration until 3 h after the administration
- Housing: individually in stainless steel cages with a stainless mesh floor (D38 cm × W24 cm × H18 cm)
- Diet: solid pellets Lab Diet #5002 (PMI Nutrition International), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Remarks on environmental conditions:
Between July 8 and 21 and July 23, 2011, the humidity in the animal room exceeded the upper control limit (70%) for 5 to 30 min per occasion, several times per day. (Abnormal humidity persisted for approximately 40 min on July 12 and 1.5 h on July 18.)
Humidity most frequently exceeded the limit on July 9 (26 episodes), and the highest humidity (79%) was observed on July 9, 14, and 18.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: carboxymethyl cellulose (CMC)
Remarks:
1% aqueous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The test substance was not homogeneously dispersible in distilled water; however, it was dispersible in 1% CMC.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: In previous acute toxicity study performed on structurally similar derivates, no animals died at a dose of 300 mg/kg bw. As the test substance was not expected to cause animal deaths at 300 mg/kg bw, the initial dose was set at 2000 mg/kg bw in accordance with the guideline.
Doses:
2000 mg/kg bw (step 1 and 2)
No. of animals per sex per dose:
6 (3 per step)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and behaviour within 30 min (0 h) and 1, 3 and 6 h after administration and further once daily for 14 days until terminal necropsy day. Body weight was measured immediately before administration (Day 0), and on Days 3, 7, and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
accordint to OECD 423 (1 dead animal in step 1)
Mortality:
One animal of step 1 was found dead on Day 1.
Clinical signs:
Immediately after administration, prone position in 1/6 animals, eyelid closure in 2/6 animals, ptosis in 3/6 animals, and decreased locomotor activity in 1/6 animals were observed.
At 1 h after administration, eyelid closure in 3/6 animals, ptosis in 1/6 animals, staggering gait in 4/6 animals, and decreased locomotor activity in 3/6 animals were observed. At 3 h after administration, ptosis in 3/6 animals, staggering gait in 3/6 animals, and decreased locomotor activity in 2/6 animals were observed.
At 6 h after administration, prone position in 1/6 animals and loss of locomotor activity in 1/6 animals were observed.
On Day 1, prone position, loss of locomotor activity, irregular respiration, hypothermia, soiled fur (red) of external genitalia, lacrimation, peri-nasal/oral smudge, and soiled fur from external genital to lower abdominal regions were observed in 1/6 animals (same animal was found dead later on Day 1).
Body weight:
Surviving animals showed steady increases in body weight. The differences in body weight of each animal administered the test substance were within ± 20% of the overall mean body weight.
Gross pathology:
Necropsy revealed a dark red area of the glandular stomach mucosa (adherence of blood-like substance) in the animal that died on Day 1 and redness of ileum mucosa and thinning of ileum mucosa in 2/5 animals sacrificed at Day 14 for terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in female rats 1/6 animals died at 2000 mg/kg bw and thus the LD50 value was > 2000 mg/kg bw.