Registration Dossier

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
Study period:
from 4 March 1981 to 3 April 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Equivalent to guideline study with acceptable restrictions. This study is read across from citric acid (CAS 77-92-9).

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:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Groups of 5 mice of each sex were given a single gavage dose with observation for mortality for 10 days. Clinical observations were made at 2 h and 24 h after treatment; body weights were only recorded prior to dosing. The observation period was 10 days instead of 14 recommended by guideline.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
other: Füllinsdorf Albino (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoffmann-La Roche & Co. Ltd, Company breeding farm: Tierfarm Füllinsdorf. (no further details)
- Age at study initiation: not stated
- Weight at study initiation: 20 g
- Fasting period before study: not stated
- Housing: 5/Macrolon type III cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50 +/- 10
- Air changes (per hr): 20-25
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: (main study) From: 1981-03-24 To:1981-04-03

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: (main study) 150-600 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw
Doses:
0, 3, 4.2, 6, 8.5, 13 g/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: clinical observations at 2 h and 24 h following treatment; observation for mortality daily for 10 days; body weights recorded only prior to treatment
- Necropsy of survivors performed: no
- Other examinations performed: none
Statistics:
probit analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 400 mg/kg bw
95% CL:
4 500 - 6 400
Remarks on result:
other: observation limited to 10 days
Mortality:
No deaths at 3 g/kg bw, death of all exposed within 24 h at 8.5 g/kg bw, and above. See table 1.
Clinical signs:
Clinical observations were limited to 2 h and 24 h after treatment; the descriptions given are very limited. See table 1.
Body weight:
No data on body weight following treatment.
Gross pathology:
Not examined.
Other findings:
None.

Any other information on results incl. tables

Table 1: Number of animals dead and with evident toxicity and time range within which mortality occurred

Dose
(g/kg bw)

Mortality (dead/total)

Time of death (within)

Overt toxicity

Combined (5 male, 5 female)*

2 h

24 h

Control

0/10

-

none

none

3

0/10

-

none

none

4.2

2/10

24 h

none

none

6

7/10

24 h

slight relaxation

none

8.5

10/10

24 h

death

-

12

10/10

24 h

death

-

* Separate data for each sex not given

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A study conducted according to a protocol that was similar to OECD 401, but limited in some respects and without GLP status, identified an acute oral LD50 value of 5.4 g/kg bw for male and female mice. The result is read across from citric acid (CAS 77-92-9).