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Description of key information

In an acute oral toxicity study, the LD50 was determined to be ca. 2200 mg/kg bw for male and female rats. In an acute inhalation toxicity study, the LC50 was determined to be >5.4 mg/L. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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other: Non-GLP, near guideline study, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, 7 day observation period instead of 14
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Gassner rats
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
- The test concentration used was 20% (w/v) in aqueous suspension with CMC.
Doses:
1000, 1250, 1600, 2000, 2500, 3200 and 4000 mg/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic examination.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 200 mg/kg bw
Based on:
test mat.
Mortality:
- 1000 mg/kg bw:: No mortality occured
- 1250 mg/kg bw.: 1 male animal died within 24 h. No aditional mortality occured.
- 1600 mg/kg bw:: 1 female animal died within 24 h. No aditional mortality occured.
- 2000 mg/kg bw:: 2 male and 1 female animals died within 24 h. No aditional mortality occured.
- 2500 mg/kg bw:: 8 male and 7 female animals died within 24 h. One aditional female animal died within 48 h.
- 3200 mg/kg bw:: All male (10) and 8 female animals died within 24 h. One aditional female animal died within 7 days.
- 4000 mg/kg bw: All male (10) and all female (10) animals died within 24 h.
Clinical signs:
Dyspnea, apathy, and lying in the abdominal and lateral position was observed.
Gross pathology:
Acute dilatation of the heart and congestive hyperemia of lung and liver was observed.
Interpretation of results:
sligthly toxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr . K . Thomae GmbH, D-7950 Biberach, FRG
- Age at study initiation: approx. 8 - 9 weeks
- Weight at study initiation: male animals 268 ± 2.5 g, female animals 189 ± 7.1 g.
- Housing: groups of five in cages type D III of Becker, without bedding.
- Diet: KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets (Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland), ad libitum.
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): Fully aircondidtioned
- Photoperiod (hrs dark / hrs light): 12 /12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
- Generation of the inhalation atmosphere: A dust aerosol was generated by means of a dosing-wheel dust generator (Gericke/BASF). The test substance was mixed with 1 wt% of Aerosil in order to achieve a more uniform dust concentration in air. The concentration was adjusted by varying rotation of the metering disc.
- The following air flow (supply air) was set: compressed air : 1500 L/h. The exposure system was placed in an air-conditioned laboratory. Temperatures in the exposure system were 19 - 25°C. By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.

Analytical method used: Gravimetric determination of the inhalation atmosphere concentration. The preweighed filter was placed into the filtration
equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drawn through the filter. The dust concentration in mg/L was calculated from the difference between the preweight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmosphere. The concentration was corrected for the amount of the additive (1 sample about hourly).
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.4 mg/L
No. of animals per sex per dose:
5
Control animals:
other: historical control for body weight
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: yes, at the end of the 14-day observation period the animals were sacrificed with CO2 and were subjected to gross-pathological examination.
Statistics:
On the basis of the binomial test (Wittig, H. : Mathematische Statistik 1974, pp. 32 - 35).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: - During exposure: accelerated respiration - After exposure and during observation period: accelerated respiration (10/10), reddish nasal (2/10) and eye discharges (1/10) (blood test positive), and fur discoloured with the test substance (10/10) was obser
Body weight:
- Mean body weight for male animals: 268 g at study start, 330 g after 14 days
- Mean body weight for female animals: 189 g at study start, 206 g after 14 days
Gross pathology:
No pathological findings noted.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

In an acute oral toxicity study, performed similarly to OECD guideline 401, 10 Gassner rats per sex per dose were exposed to 1000, 1250, 1600, 2000, 2500, 3200 and 4000 mg/kg bw of the test substance (BASF 1971). No mortality occurred in the 1000 mg/kg group. One animal died in the 1250 and 1600 mg/kg group. In the 2000 mg/kg group 3 animals died and 16, 19 and 20 in the 2500, 3200 and 4000 mg/kg exposure groups respectively. The observation period after exposure was only 7 days instead of the recommended 14 days. However, almost all mortality occured within the first 24 hours. Additional mortality after 7 days is therefore likely to be minimal. A time depended change in LD50 value is not expected.

Acute inhalation toxicity

In an acute inhalatory toxicity test performed according to OECD guideline 403, 5 Wistar rats per sex were exposed to 5.4 mg/L anthranilamide as aerosol (BASF 1990). After the 14-day observation period no mortality had occurred. During exposure accelerated respiration was observed while after the 4 hour exposure period animals showed accelerated respiration, reddish nasal and eye discharges (blood test positive), and discolored fur. These effects were absent one day after exposure. No pathological findings were noted. The LC50 was determined to be greater than 5.4 mg/L air.

In an additional acute inhalation study in which the inhalatory toxicity of the test substance was assessed, 6 male and 6 female rats were exposed to 0.009 mg test substance/L air for 8 hour (BASF 1971). No mortality occurred and no clinical signs were observed. No gross pathology findings were noted.

Justification for classification or non-classification

Based on an oral LD50 in rats of > 2200 mg/kg bw classification for acute oral toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Based on an inhalation LC50 of > 5.4 mg/L air classification for acute inhalation is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.