Registration Dossier

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:
other: Basic data given, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): tert.-butylamine, substance no. 84/396
- Analytical purity: 98%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Fasting period before study: 16 hours
- Housing: groups of 5 in stainless steel wire mesh cages type DK-III
- Diet: Kliba laboratory diet, Klingenthalermuehle AG, Kaiseraugst, Switzerland ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 3.61, 4.64, 6.81 (w/v), respectively
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
316, 464, 681 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 316 - < 464 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
514 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 464 mg/kg bw
Mortality:
681 mg/kg dosing group: 5/5 females, 4/5 males (d 1-d 14)
464 mg/kg dosing group: 1/5 females, 5/5 males (d 1-d 14)
316 mg/kg dosing group: no death occurred
Clinical signs:
dyspnoea, apathy, staggering, tremors, piloerection, diarrhea, salivation, stretching, imbalance, poor general condition
Body weight:
body weight gain reported for the lowest dosing group (day 14 males 71 g, females 37 g), survivors of the other dosing groups showed body weight lost during day 1 and day 7 of the study and started to gain weight again in the second week of the observation period
Gross pathology:
mid and high dosing groups:
haemorrhagic gastritis, bloody content of intestine, acute peritonitis, local adhesions of stomach and liver, single animals with acute serous peritonitis as a result of perforation of the stomach, single animals with very severe tymanitas, one animal with perforated duodenal ulcer, swollen margo plicatus (cuticular ridge)

lowest dosing group:
1 male with acute lung emphysema and haemorrhagic intestinal content, other animals without findings

Applicant's summary and conclusion