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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-phenylimidazole
EC Number:
211-581-7
EC Name:
2-phenylimidazole
Cas Number:
670-96-2
Molecular formula:
C9H8N2
IUPAC Name:
2-phenylimidazole

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 260 g (males); 210 g (females)
- Diet: Herilan MRH-Haltung, Alleinfuttermittel für die Haltung von Mäusen, Ratten und Hamstern (Heinrich Eggersmann KG, Rinteln, Germany)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5% aqueous CMC formulation
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
215, 316, 464, 681, 1000 and 1470 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 and weighing: The animals were observed for signs of toxicity and mortality immediately, 15 and 30 min, 1, 2, 4 and 5 h after dosing, and thereafter once daily. The body weight was recorded prior to treatment for all dose levels, and on day 3, 7 and 13 for all dose levels except of the highest dose levels.
- Necropsy of survivors performed: yes, the animals were histopathologically examined.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Based on:
test mat.
Mortality:
1470 mg/kg bw: 5/5 males (1/5 each at 15 and 30 min post-dose, and at 2 h post-dose, respectively; and 2/5 at day 1 post-dose) and 5/5 females (3/5 at 30 min post-dose and 2/5 1 h post-dose) died
1000 mg/kg bw: 2/5 males (at day 1 post-dose) and 3/5 females (1/5 at 4-h postdose and 2/5 at day 1 post-dose) died
681 mg/kg bw: 2/5 males (1/5 each 2 h and 4 h post-dose, respectively) and 2/5 females (at 4 h post-dose) died
464 mg/kg bw: 0/5 males and 0/5 females died
316 mg/kg bw: 0/5 males and 0/5 females died
215 mg/kg bw: 0/5 males and 0/5 females died
Clinical signs:
1470 mg/kg bw: distinct irregular breathing, distinct and severe apathy, distinct and severe atony, slight and distinct redness of the skin and distinct exsiccossis were observed immediately after dosage.
1000 mg/kg bw: distinct irregular breathing were observed immediately after dosage (15 and 30 min), at 2 and 4 h post-dose and at day 3 and 4 post-dose, respectively. Slight apathy and distinct stagger was noted at day 3 and 4 post-dose. Occasionally distinct lateral position and distinct redness of the skin were noted immediately after dosage (15 and 30 min), at 2 and 4 h post-dose, respectively. Distinct ruffled fur was seen at day 3 and 4 post-dose.
681 mg/kg bw: slight and distinct irregular breathing were observed 30 min after dosage, at 2 and 4 h post-dose and at day 1 post-dose, respectively. Slight and distinct apathy was noted immediately after dosing, and at 1, 2 and 4 h, at day 1 post-dose. Occasionally distinct lateral position was noted immediately after dosage (15 and 30 min), at 2 and 4 h post-dose, respectively. Occasionally distinct stagger occurred immediately after dosing, and at 1, 2 and 4 h and at day 1 post-dose. Occasionnally distinct atony occurred 30 min, 1, 2 and 4 h post-dose. Occasionally distinct narcosis-like conditions and partially missing pain reaction were noted at 2 and 4 h post-dose. Occasionally distinct spasticity at 2 and 3 d post-dose.
464 mg/kg bw: Distinct irregular breathing, distinct and severe apathy, distinct atony and distinct lateral position were observed after dosing. Spastic gait was noted at 4- and 5-h post-dose and on day 1 after dosing.
316 mg/kg bw: Distinct irregular breathing, slight and distinct apathy, distinct atony and distinct lateral position were observed after dosing. Spastic gait was noted at 4- and 5-h post-dose.
215 mg/kg bw: Slight apathy was observed after dosing. Spastic gait was noted at 4- and 5-h post-dose and on day 1 after dosing.
Body weight:
In females, a reduction of the body weight was observed in the beginning of the observation period.
Gross pathology:
1470 mg/kg bw: heart: dilation of the right ventricle, acute hyperemia
1000 mg/kg bw: heart: dilation of the right ventricle, acute hyperemia; liver: marbled surface, peripheral lobular pattern of the liver; stomach: atonic with substance; intestine: slightly reddened intestinal mucosa; bladder: high filling
681 mg/kg bw:without findings
464 mg/kg bw: without findings
316 mg/kg bw: without findings
215 mg/kg bw: without findings

Applicant's summary and conclusion

Interpretation of results:
other: Acute oral 4, H302 according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: Acute oral 4, H302