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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study conducted prior to GLP, no guideline followed as none was available in 1982 (OECD 401: 1987). However, the available information is documented sufficiently and allows the conclusion that the study was properly conducted with a scientifically acceptable method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
p-tert-butylaniline
EC Number:
212-215-9
EC Name:
p-tert-butylaniline
Cas Number:
769-92-6
Molecular formula:
C10H15N
IUPAC Name:
p-tert-butylaniline
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeder: Winkelmann, Borchen
- Age at study initiation: ca. 9 weeks
- Weight at study initiation: 173 g (average)
- Housing: In groups of five in Makrolon cages type III on low-dusting wood pellets
- Diet (e.g. ad libitum): Altromin R 1324 (Altromin GmbH und Co KG, Lage) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 ± 5%
- Photoperiod (hrs dark / hrs light): 12 / 12 (artificial light from 7 am to 7 pm)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.5 mL/kg (=472 mg/kg)
0.6 mL/kg (=566.4 mg/kg)
0.65 mL/kg (=613.6 mg/kg)
0.8 mL/kg (=755.2 mg/kg)
1.0 mL/kg (=944 mg/kg)
1.2 mL/kg (=1132.8 mg/kg)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times on application day, otherwise twice a day for clinical symptoms, weighing on day 0 and 14
- Examinations performed: clinical signs, body weight, autopsy (randomly)
Statistics:
The LD50 (confidence interval for p ≤ 0.05) value was calculated by programmed probit analysis according to Fink & Hund (Arzneim.-Forsch. 15, 1965, 624).

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
0.68 mL/kg bw
Based on:
test mat.
Remarks on result:
other: =642 mg/kg bw
Mortality:
Animals died in all dose groups except for the lowest dose group.
Clinical signs:
Poor general conditions, cyanosis, prone/lateral position, narcosis, slight reflexes, ruffled fur, bloody and watery eyes.
Body weight:
No information available.
Gross pathology:
All animals killed after 14 days and animals that died during the test were without pathological findings.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The study was conducted similar to OECD guideline 401 on the registered substance itself [1981 prior to GLP, no guideline followed as none was available (OECD 401: 1987)]. The available information is documented sufficiently and allows the conclusion that the study was properly conducted with a scientifically acceptable method. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The determined LD50 value is 0.68 mL/kg bw (=642 mg/kg bw). The result is suitable to determine the classification of the substance; according to Regulation (EC) No. 1272/2008, the substance has to be classified as acute toxic cat. IV.
Executive summary:

In an acute oral toxicity study (no GLP) from 1981 similar to the later OECD Guideline 401, groups of 9 weeks old, male Wistar rats (10/dose) were given oral doses (0.5 mL/kg =472 mg/kg; 0.6 mL/kg =566.4 mg/kg; 0.65 mL/kg =613.6 mg/kg; 0.8 mL/kg =755.2 mg/kg; 1.0 mL/kg =944 mg/kg; 1.2 mL/kg =1132.8 mg/kg; via gavage) of the test substance and observed for 14 days.

 

Oral LD50 = 0.68 mL/kg bw = 642 mg/kg bw; the test substance has to be classified as acute toxic cat. IV according to CLP.

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