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Administrative data

Description of key information

LD50 (oral) > 5000 mg/kg bw, 
LC50 (inhalation) > 179 mg/kg bw, 
LD50 (dermal) > 2025 mg/kg bw.

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
Study period:
August 27, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: 84/449/EEC; L251
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Male (158 - 180 g)
- Diet (e.g. ad libitum): ad libitum untill 16 h before the administration
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
Single dose: 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice a day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, negroscopy
Statistics:
ROSIELLO et al.: J. Tox. Environ. Health.: 3, 797 (1977)
The method is based on Maximum-Likelihood-method: BLISS: Q.J.Pharm. Protocol. : 11, 192 (1938)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Clinical signs:
other: No clinical signs observed
Gross pathology:
No abnormalities observed

Table of results:

dosis (g/kg bw) sex dead animals symptomatic animals survivors
5.0  (male) 0 0 5
5.0  (female) 0 0 5

Weight table:

female # week
  0 1 2
1 182 185 184
2 185 192 193
3 190 186 189
4 186 189 188
5 188 189 190
male # week
  0 1 2
1 180 210 227
2 163 186 210
3 165 202 230
4 158 181 200
5 158 180 200
Interpretation of results:
other: CLP criteria not met
Conclusions:
LD50 (male/female) > 5000 mg/kg bw
Executive summary:

The substance to be registered has been tested according to EU Method B.1. During the study ten rats have been used (5 male and 5 female) for testing a single dose of 5000 mg/kg bw. No deaths occurred during the test and no abnormalities were seen in autopsy. The test item has shown a LD50 > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
According to internationally accepted testing guidance

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
Study period:
March 22, 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
GLP compliance:
no
Remarks:
Pre GLP.
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: ARS/Sprague - Dawley, Madison, Winsconsin
- Age at study initiation:
- Weight at study initiation: 153 g
- Fasting period before study: fasted during exposition
- Housing: individually in stock cages
- Diet (e.g. ad libitum): standard laboratory diet with Purina Rat Chow, Ralston Purina Company, St. louis, Missouri
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23°C
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass inhalation chamber
- Exposure chamber volume: 70 liters
- Method of holding animals in test chamber:
- Source and rate of air: Dust feeder, rate of air: 6.4 L/min
- Method of particle size determination: microscopic determination
- Temperature, humidity, pressure in air chamber: 25 °C, 29.92 inches Hg

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 1 - 5 microns : 34%; 6 - 25 microns: 58%; 26 - 615 microns: 8%
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
179 mg/m3 air
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 179 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred
Clinical signs:
other: No evidence
Body weight:
Within the normal limits, average two-week body weight gain was 57g
Gross pathology:
Minimal to mild focal red discoloration of the lungs in all rats
Other findings:
No untoward behavioral reactions

Particle Size Distribution data:

Particle size range
(microns)		 N. of Particles counted % of total counted
1 - 5 152 34
6 - 25 263 58
26 - 615 35 8
Conclusions:
LC50 (male/female) > 179 mg/m3 air
Executive summary:

The substance to be registered has been tested according a procedure similar to OECD 403. During the study the concentration of 179 mg/m3 air has been tested on ten rats (5 male and 5 female). After the 14 days observation period there were no deaths, no untoward behavioural reactions or adverse body weight effect. Necroscopy revealed minimal to mild red discoloration in the lungs of all rats. In these experimental conditions the test substance has shown a LC50 > 179 mg/m3 air.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
179 mg/m³ air
Quality of whole database:
Method equivalent or similar to guidelines internationally accepted.

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
Study period:
February 26, 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
Number of animals: 4 rabbits (2 male and 2 female)
GLP compliance:
no
Remarks:
Pre GLP.
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: New Zeland
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.94 - 3.2 g
- Housing: individually in suspende, wire - bottomed cagesand maintained on a standard laboratory ration
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- % coverage: 30%
- Type of wrap if used: plastic wraptaped in place

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24h
Duration of exposure:
24 h
Doses:
2025 mg/kg bw
No. of animals per sex per dose:
2 male and 2 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Initial and final body weight recorded
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, behavioral abnormalities.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 025 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Clinical signs:
other: No untoward behavioral reactions were noted
Gross pathology:
No gross pathologic alterations revealed
Other findings:
A bright blue stain noted at the 24h, 7d and 14d observations

Mortality and body weight data:

dose
mg/kg bw		 animal  individual body weight n° dead/
n°tested		 % dead
n° sex day n° 0 day n° 14
2025 1 m 3.2 3.24 0/4 0
2 m 2.94 2.6
3 f 3.2 3.2
4 f 3.2 3.24
Interpretation of results:
other: CLP criteria not met
Conclusions:
LD50 (male/female) > 2025 mg/kg bw
Executive summary:

The substance to be registered has been tested according a procedure similar to OECD 402, during the study the single dose 2025 mg/kg bw has been tested on 4 rabbits (2 male and 2 female). After the 14 days observation period there were no deaths , untoward behavioral reactions or adverse body weight effect. A bright blue stain was noted at the contact site at 24h, 7d, 14d observations. Necroscopy revealed no gross pathologic alterations among any animals. In these experimental conditions the test item shows a LD50 > 2025 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 025 mg/kg bw
Quality of whole database:
Method equivalent or similar to guidelines internationally accepted.

Additional information

A study on intraperitoneal acute toxicity was conducted in 1982 but only a short summary is available. During the study, the test substance showed a high value for median lethal dose (LD50 = 1790 mg/kg bw).


Justification for classification or non-classification

According to the CLP Regulation (EC) n. 1272/2008 Acute toxicity means those adverse effects occurring following oral or dermal administration of a single dose of a substance or a mixture, or multiple doses given within 24 hours, or an inhalation exposure of 4 hours.

The test subsatnce is not classified according to tables 3.1.1 and 3.1.2 of the CLP Regulation.