Registration Dossier

Administrative data

Description of key information

The acute oral LD50 was performed following OECD 401 using Sprague-Dawley rats; however only two dose levels were used. The LD50 was not closely defined. However, in another oral study (a sighting study for test 4.2.1) more than 50% of rats died within one day of receiving a dose of 1000 mg/kg. Thus the LD50 is 500-1000 mg/kg. 
The inhalative LC50 study was performed following a modified Annex V limit test. A limit concentration of 2.6 mg/l was used because the results of the acute oral test suggested to the test laboratory that all animals would die if exposed to 5 mg/l. The marked weight loss and severe respiratory effects noted at 2.6 mg/l supported this prediction. Sprague-Dawley rats were used in this test, test item was applied as liquid aerosol to snout only. No mortality was noted besides of the clinical signs mentioned above. Gross pathology showed pale discoloration of the lungs in 4 out of ten animals.
The LD50 was performed similar or equal to OECD 402 using rabbits; one dose level was tested and four animals used. The acute dermal LD50 was found to be > 5000 mg/kg.
Based on these findings, the substance is classified as Harmful / Acute Tox. IV.

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:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: test data from ELINCS-notification obtained from ECHA on 10-June-2010 (EC-no. 405-740-1 / notification-no. 91-06-0255-00); performed under GLP and according to EU-testing methods
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
; only two dose levels
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
Dose levels of 500 and 5000 mg/kg were tested.
No. of animals per sex per dose:
5 animals per sex and dose group.
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Based on:
test mat.
Mortality:
Males:
- 500 mglkg bw; Number of animals: 5; Number of deaths: 1
- 5000 mglkg bw; Number of animals: 5; Number of deaths: 5

Females:
- 500 mglkg bw; Number of animals: 5; Number of deaths: 0
- 5000 mglkg bw; Number of animals: 5; Number of deaths: 5
Clinical signs:
Signs of toxicity related to dose levels:
- Deaths occured in all animals at 5000 mg/kg and one male at 500 mg/kg; all were within one day of dosing.
- Prior to deaths sedation was noted, other less frequent signs included convulsions.
- One survivor at 500 mglkg had subdued, hunched appearance, piloerection and soiled coat on day 1 and 2.
Body weight:
No data
Gross pathology:
Effects on organs:
- No treatment-related macroscopic findings were reported.

In this study, with only two dose levels, the LD50 was not closely defined. However, in a dose-range finding study performed for a repeated dose toxicity test, more than 50% of rats died within one day of receiving a dose of 1000 mg/kg. Thus the LD50 is 500-1000 mg/kg.

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The combined acute oral LD50 on rats was determined to be 500-1000 mg/kg.
Executive summary:

The LD50 was performed following OECD 401 using Sprague-Dawley rats; however only two dose levels were used. The LD50 was not closely defined. However, in a dose-range finding study performed for a repeated dose toxicity test, more than 50% of rats died within one day of receiving a dose of 1000 mg/kg. Thus the LD50 is 500-1000 mg/kg and the substance is classified as Harmful / Acute Tox. IV.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: test data from ELINCS-notification obtained from ECHA on 10-June-2010 (EC-no. 405-740-1 / notification-no. 91-06-0255-00); performed under GLP and according to EU-testing methods
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
A limit concentration of 2.6 mg/l was used because the results of the acute oral test suggested to the test laboratory that all animals would die if exposed to 5 mg/l.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
other: snout only
Vehicle:
air
Details on inhalation exposure:
Mass median aerodynamic diameter (for liq.+solid aerosol):
Mass mean aerodynamic diameter 6.2 mcrometers; 25.5% of droplets were less than 3.5 micrometers in diameter
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
A limit concentration of 2.6 mg/l was used because the results of the acute oral test suggested to the test laboratory that all animals would die if exposed to 5 mg/l.
No. of animals per sex per dose:
5 animals per sex and dose group.
Control animals:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Males: 2.6 mg/L; number of animals: 5; Number of deaths: 0
Females: 2.6 mg/L; number of animals: 5; Number of deaths: 0
Clinical signs:
other: In all animals there was no response to audio/physical stimuli on day 1, and abnormal respiration (very severe up to day 3), subdued behaviour and umkempt appearance until day 8-11. The severe respiratory effects noted post exposure included gasping, crac
Body weight:
Weight loss (by up to 30%) occurred in all animals during day 1 to 4.
Gross pathology:
Pale colouration of lungs was reported in 4/10 animals.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Tle combined acute inhalative LC50 on rats was determined to be > 2.6 mg/L air.
Executive summary:

This LC50 study was performed following a modified Annex V limit test. A limit concentration of 2.6 mg/l was used because the results of the acute oral test suggested to the test laboratory that all animals would die if exposed to 5 mg/l. The marked weight loss and severe respiratory effects noted at 2.6 mg/l supported this prediction. Sprague-Dawley rats were used in this test, test item was applied as liquid aerosol to snout only. No mortaslity was noted besides of the clinical signs mentioned above. Gross pathology showed pale discoloration of the lungs in 4 out of ten animals.

Based on these findings, the substance is classified as Harmful / Acute Tox. IV.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
2 600 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
August-December 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no guideline study; not GLP-compliant
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Principles of method if other than guideline:
four animals used
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
no data
Duration of exposure:
24 hours
Doses:
Dose level: 5000 mg/kg
Dose volume: 4.1 ml/kg
No. of animals per sex per dose:
4 animals
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
No clinical signs noted
Body weight:
No changes on body weights observed
Gross pathology:
No pathological findings noted
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 on rabbits was found to be > 5000 mg/kg.
Executive summary:

The LD50 was performed similar or equal to OECD 402 using rabbits; one dose level was tested and four animals used. The acute dermal LD50 was found to be > 5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Reliable data from ELINCS-notification (Klimisch 1)

Justification for selection of acute toxicity – inhalation endpoint
Reliable data from ELINCS-notification (Klimisch 1)

Justification for selection of acute toxicity – dermal endpoint
Reliable data from ELINCS-notification (Klimisch 2)

Justification for classification or non-classification

Based on the data available the substance needs to be classified and labelled as follows:

Regulation (EC) No 1272/2008

Signal word: Danger

Acute toxicity; Category 4 ; Oral

H302 Harmful if swallowed

Acute toxicity; Category 4 ; Inhalation

H332 Harmful if inhaled

Directive 67/548/EEC / 1999/45/EC

Xn, harmful

R20/22 - Harmful by inhalation and if swallowed