Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles (non-GLP) For read-across justification refer to section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Principles of method if other than guideline:
BASF-TEST: In principle, the methods described in the OECD Guideline 401 were used. Young adult laboratory rats were purchased from breeder. Several groups of 10 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight was determined before the start of the study as well as after day 2, 5, 7 and 13
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Lot/batch No.: 03370
- Purity: 75%
- Impurities (identity and concentrations): 8% Na3 Ethylenediaminetriacetic acid, 1.2% Na2 Ethylenediaminetriacetic acid, 3.6% Na3 Nitriloltriacetic acid, < 0.3% Na2 iminodiacetic acid, 2.6% Na-glycolic acid, urotropin
- Expiration date of the lot/batch: April 1984
- Physical state: solid powder

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
- Weight at study initiation:
1210 mg/kg bw: 179 g males/178 g females
1780 mg/kg bw: 188 g males/180 g females
2000 mg/kg bw: 180 g males/182 g females
2610 mg/kg bw: 188 g males/187g females
- Housing: 5 animals per cage
- Diet: Ssniff R ad libitum):
- Water: ad libitum
- Acclimation period: at least one week
- Fasting period before study: 16 h

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION
- Stock solutions prepared:
12.1% for the 1210 mg/kg bw dose group
17.8% for the 1780 mg/kg bw dose group
20.0% for the 2000 mg/kg bw dose group
26.1% for the 2610 mg/kg bw dose group

DOSE VOLUME APPLIED:
10 ml/kg bw
Doses:
1210 mg/kg bw; 1780 mg/kg bw; 2000 mg/kg bw; 2610 mg/kg bw
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: daily
- Frequency of weighing: prior to the start of the experiment and on day 2, 5, 7, 13
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 913 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
1 780 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 780 - < 2 000 mg/kg bw
Mortality:
No mortalities were observed in the lowest dose group. At 2000 mg/kg bw all females and 7/10 males died (see table 1). In the highest dose group still falf of the males survived.
Clinical signs:
1210 mg/kg bw: no effects
1780 mg/kg bw: males dyspnea, aphathy, ataxia, shaggy fur, poor general state; fully revesible within 5 days /females dyspnea, aphathy, ataxia, abnormal positions, spastic gait, exiccosis, diarrhea, shaggy fur, saliva, poor general state; fully reversible within 1 day
2000 mg/kg bw: males dyspnea, aphathy, ataxia, shaggy fur, poor general state; fully revesible within 1 day/females dyspnea, aphathy, ataxia, atony, exiccosis, poor general state
2610 mg/kg bw: males dyspnea, aphathy, ataxia, aggressivness, diarrhea, piloerrection, poor general state; fully revesible within 1 day/females: dyspnea, aphathy, ataxia, atony, shaggy fur, poor general state
Body weight:
1210 mg/kg bw: body weight gain male 106 g/ 46 g female
1780 mg/kg bw: body weight gain male 95 g/ 47 g female
2000 mg/kg bw: body weight gain male 93 g
2610 mg/kg bw: body weight gain male 97 g
Gross pathology:
Animals that died:
stomach: redness and/or bloody ulceration of the glandular part of the stomach, redness of the mucous membran, general hyperemia
gut: atonic, redness of the mucous membran, bloody mucous content, general hyperemia

Animals which were sacrificed:
nothing abnormal detected

Any other information on results incl. tables

Table 1: Mortalies of rats after oral application of Na4EDTA

1210 mg/kg bw 1780 mg/kg bw 2000 mg/kg bw  2610 mg/kg bw
1 h male  0/10 0/10 3/10 0/10
female 0/10 0/10 1/10 6/10
24 h male  0/10 2/10 7/10 5/10
female 0/10 4/10 10/10 10/10
48 h male  0/10 2/10 7/10 5/10
female 0/10 4/10 10/10 10/10
7 d male  0/10 2/10 7/10 5/10
female 0/10 4/10 10/10 10/10
14 d male  0/10 2/10 7/10 5/10
female 0/10 4/10 10/10 10/10

Applicant's summary and conclusion