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Description of key information

Since the results of the acute oral and dermal toxicity studies revealed a LD50 of > 10000 mg/kg bw and > 2500 mg/kg bw, respectively, it can be concluded  that the test item has a low acute toxicity. Similar results were obtained in the acute inhalation toxicity study and by the administration via intraperitoneal injection. Thereby no mortality was observed and a LC0 of 0.68 mg/L (inhalation) and a LD50 of > 10000 mg/kg bw (intraperitoneal injection) was determined. 

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: Comparable to guideline study with acceptable restrictions (incomplete documentation)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(application volume exceeded 20 mL/kg bw in the highest dose group, 2 dose groups, 7 day observation period)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Weight range at study initiation: 185 -250 g (males); 164 - 196 g (females)

ENVIRONMENTAL CONDITIONS: not reported
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
aqueous suspension in 0.5% CMC
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 35% (10000 mg/kg bw), 15% (1000 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 28.6 mL/kg bw

Doses:
1000 mg/kg bw (6.7 mL/kg bw) and 10000 mg/kg bw (28.6 mL/kg bw)
No. of animals per sex per dose:
5 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations after application: day 0 (after 2-3 hours) and once daily on working days
- Frequency of weighing: before application, on day 2 - 3 and at termination
- Necropsy of survivors performed: yes
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 1/10 animal died on day 2 of observation
Mortality:
10000 mg/kg bw: 1 animal (female) died on day 2 of observation
1000 mg/kg bw: no mortality
Clinical signs:
10000 mg/kg bw: On day 1, blue colouring of faeces and slight apathy were observed. Within 2 days, the symptoms were fully reversed.
1000 mg/kg bw: On day 1, blue colouring of faeces was observed. On day 2, faeces colour was normal.
Body weight:
There was no test item-related effect on body weights.
10000 mg/kg bw: males: 197 g (day 0), 218 g (day 2) and 216 g (day 8); females: 171 g (day 0), 179 g (day 2) and 171 g (day 8)
1000 mg/kg bw: males: 228 g (day 0), 267 g (day 3) and 256 g (day 8); females: 187 g (day 0), 200 g (day 3) and 189 g (day 8)
Gross pathology:
10000 mg/kg bw: animal that died: substance residue was found in the thorax. No abnormalities were found in the other animals.
1000 mg/kg bw: no abnormalities were found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiencies (unsuitable vapour/dust generating system: animals were not sufficiently exposed)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(whole body exposure for 8 h, no analytics to determine concentrations or particle size distribution, 8 day observation period)
Principles of method if other than guideline:
BASF test (IHT):
The test demonstrates the toxicity of an atmosphere enriched with dust of the test substance at room temperature. Young adult laboratory rats, 6 per sex, were exposed sequentially to the dust generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 7 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period.
GLP compliance:
no
Test type:
other: inhalation hazard test
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation (mean values): males: 203 g, females: 178 g (group #1); males: 179 g, females: 193 g (group #2); males/females: 183 g (control group)

ENVIRONMENTAL CONDITIONS: not reported
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: exsiccator
- Source and rate of air: 200 L/h
- Temperature in air chamber: 20°C
- System of generating particulates/aerosols: bubbling 200 L/h air through a substance column


TEST ATMOSPHERE
- Brief description of analytical method used: reweighing of a substance column
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle: air
- Concentration of test material in vehicle: 0.68 mg/L (nominal conc.)

Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
8 h
Concentrations:
0.68 mg/L (nominal)
(Nominal concentration was calculated as quotient of the amount of test substance weight loss during the exposure and the amount of air used during the exposure.)
No. of animals per sex per dose:
Test group: 6 rats
Control group: 3 rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 8 days
- Frequency of weighing: before application and before sacrifice (day 8)
- Necropsy of survivors performed: yes
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.68 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Mortality:
No mortality was observed.
Clinical signs:
other: The animals showed slight irritations of mucous membrane which were reversible within 3 days.
Body weight:
Body weight were considered unaffected by the treatment with the test item.
Mean weight before application:
Test group#1: males: 203 g, females 178 g; test group#2: males: 179 g, females: 193 g; control group: males/females: 183 g
Mean weight before sacrifice:
Test group#1: males: 233 g, females 192 g; test group#2: males: 200 g, females: 202 g; control group: males: 226 g, females: 192 g
Gross pathology:
No abnormalities were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (incomplete documentation, occlusive treatment)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(occlusive treatment)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Wiga
- Weight range at study initiation: 135 - 161 g (males); 116 - 119 g (females)

ENVIRONMENTAL CONDITIONS: not reported

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 cm²
- % coverage: > 10 %
- Site of exposure: right back

REMOVAL OF TEST SUBSTANCE
- Washing: with water containing mild detergent


TEST MATERIAL
- Amount applied: 2500 mg/kg bw (5 mL/kg bw)
- Concentration (if solution): 50 % (in water)
- For solids, paste formed: yes

Duration of exposure:
24 h
Doses:
2500 mg/kg bw
No. of animals per sex per dose:
5 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: before application
- Frequency of observations: daily (on working day) day 1, 2, 5, 6, 7, 8, 9, 12, 13 and 14
- Necropsy of survivors performed: yes
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
No mortality was observed.
Clinical signs:
No local or systemic signs of toxicity were observed. Only substance residues (light-blue) on the skin were seen during the whole observation period.
Body weight:
Changes in body weight are not documented.
Mean weights at initiation: 151 g (males); 117 g (females)
Gross pathology:
No abnormalities were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 500 mg/kg bw

Additional information

Acute oral toxicity

In the key acute oral toxicity study (BASF AG, 1976/2002, equivalent to OECD 401), groups of 5 Sprague-Dawley rats per dose level were exposed by single oral gavage to the test item (vehicle: carboxymethyl cellulose) in concentrations of 1000 mg/kg bw (6.7 mL/kg bw) and 10000 mg/kg bw (28.5 mL/kg bw). Animals were observed for 7 days. One animal died at the highest dose group. Gross pathology revealed substance residue in the thorax of the death animal. Blue colouring of faeces was observed in all dose groups which was fully reversible within two days. The oral LD50 was determined to be > 10000 mg/kg bw in male and female rats.

Acute inhalation toxicity

In an acute inhalation toxicity study (BASF AG, 1979/2002, equivalent to OECD 403), a group of three rats was exposed by inhalation route (whole body) to the test item for 8 hours at a single concentration of 0.68 mg/L (nominal concentration was calculated as a quotient of the amount of test substance weight loss and the amount of air used during exposure). A control group was treated only with air. Animals then were observed for 8 days. No animal died. The animals showed slight irritations of mucous membranes which were reversible within 3 days. The LC0 was 0.68 mg/L (nominal) after 8 hours.

Acute dermal toxicity

In an acute dermal toxicity study (BASF AG, 1976, equivalent to OECD 402) the potential of the test item to exert systemic toxicity was examined in groups of five Sprague-Dawley rats that were occlusively exposed for 24 hours and then observed for 14 days. Animals applied 2500 mg/kg bw (5 mL/kg bw). No animal died and no local or systemic signs were observed. The identified LD50 value was > 2500 mg/kg bw in male and female rats.

Other route

In an acute toxicity study (BASF AG, 1976) the test item was administered to 5mice/sex via intraperitoneal injection at a dose of 10000 mg/kg bw. Observation period was until day 7 following treatment. No mortality was observed. Gross pathology revealed intraabdominal substance residues and sporadic adhesions. Up to 2 days after application clincial signs were observed like dyspnoea, tremor and hunched body posture. Five days after application clinical signs were fully reversed. The LD50 was determined to be > 10000 mg/kg bw in male and female mice.


Justification for selection of acute toxicity – oral endpoint
most reliable study

Justification for selection of acute toxicity – inhalation endpoint
most reliable study

Justification for selection of acute toxicity – dermal endpoint
most reliable study

Justification for classification or non-classification

Based on the results of all acute toxicity studies the test item does not need to be subjected to classification and labelling according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP/GHS).The test item does not meet the criteria for specific target organ toxicity after single exposure (STOT SE) according to Regulation (EC) No 1272/2008 (CLP).