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Description of key information

LD50 oral acute rat > 3600 mg/Kg bw

LC50 oral inhalation rat > 5.61 mg/L

LD50 dermal acute rat > 850 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:
Since February 11,1986 to February 25,1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Some details lacking, but study performed in GLP, following official guidelines
Qualifier:
equivalent or similar to
Guideline:
other: EC Directive 84/449 (Official Journal of the European Communities 27, 1984, L 251, 96).
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Winkelmann
- Age at study initiation: males 9 weeks , females 14 weeks
- Weight at study initiation: males 155-170, females 171-178 g.
- Housing:The rats were conventionally housed in cages Makrolon type III with chip wood pellets , 5 rats for each cage
- Fasting period before study:no, the was wasn't available approximately 16 hours before until 4 hours after application
- Diet: Altromin R 1324 ad libitum
- Water : tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 2 ° C
- Humidity (%): 50 ± 10%
- Photoperiod : 12 hours cycle dark/light from 6 AM to 18 CET PM
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:20 ml / kg
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 animals x sex x single dose
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 with diethyl ether
- Other examinations performed: clinical signs,

Upon application and at the end of the 14-day observation period the surviving animals were weighed individually.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 600 mg/kg bw
Based on:
act. ingr.
Mortality:
no mortality observed
Clinical signs:
no signs observed
Body weight:
no data
Gross pathology:
no pathology observed
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 for Direct Brown 44 is greater then 5000 mg/kg bw (LD50 > 3600 mg/kg bw based on active ingredient). No signs of toxicity was observed
Executive summary:

Direct Brown 44 was tested for acute toxicity with oral administration on male and female Wistar rats. The LD50 for male and female rats was greater than 5000 mg / kg body weight. There were no signs of toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 600 mg/kg bw
Quality of whole database:
The database is good, because several studies have been performed on the substance confirming the same outcome

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
other: read across from analogue substance
Adequacy of study:
weight of evidence
Study period:
19. Apr 1978 - 05. May 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is old and performed on a similar substance.
Principles of method if other than guideline:
Inhalation Hazard Test: The test was performed equivalent or similar to the method described in H.F. Smyth et. al. Am. Ind. Hyg. Ass. 23, 95-107 (1962). Inhalation of an atmosphere enriched at room temperature with the dust of the test material by rats for 7 hours. The documentation of clinical signs was performed over a period of 7 days.
GLP compliance:
no
Test type:
other: Inhalation hazard test.
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 185 g (mean), female: 221 g (mean)
Route of administration:
inhalation: dust
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- pressure in air chamber: 1.013 bar

Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 7 h
Concentrations:
7.91 mg/l (nominal)
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.61 mg/L air
Based on:
act. ingr.
Exp. duration:
7 h
Mortality:
No mortality was observed.
Clinical signs:
other: 7 h post exposure occured irregular respiration, bloody nose discharge and scrubby fur. 6 days post exposure all animals were considered as normal.
Gross pathology:
No abnormalities were observed.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Since no mortality has been observed at doses > 5 mg/L of substance in powder form, the substance is not classified for acute inhalation toxicity
Executive summary:

An inhalation toxicity test has been performed on rat exposed to dust in a concentration of 5.61 mg/L of active ingredient for 7 hours. The animals of both sex have been observed for 7 days after exposure and the effects reported

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 610 mg/m³
Quality of whole database:
The test is old and the summary lacking of many data.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
other: read across from analogue substance
Adequacy of study:
weight of evidence
Study period:
17. Apr 1974 - 02. May 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Principles of method if other than guideline:
BASF-Test. The study was performed according to: Noakes D.N. and Sanderson D.M., A Method for Determining the Dermal Toxicity of Pesticides. Brit. Journ. Ind. Med. 26, 59, 1969.
5 animals were treated for 4 or 24 h using occlusive conditions. An application site of 50 cm² was covered with the test substance and the trunk of the rat was encircled with a strip of plaster (2 layers). After the exposure time the skin was washed with detergent and water. The animals were observed 8 days and skin changes were recorded daily.

GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA
- Weight at study initiation: male: 144g (mean); female: 134g (mean)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 cm²

REMOVAL OF TEST SUBSTANCE
- Washing: After the exposure time the skin was washed with detergent and water.

TEST MATERIAL
- Concentration (if solution): 100%
- Constant concentration used: yes

Doses:
5 ml/kg (equivalent to 5000 mg/kg)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were weighted prior to exposure and symptoms were recorded daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: see overall remarks.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 850 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality was observed.
Clinical signs:
No abnormal clinical signs could be observed. All animals obtained local staining (brown) from residual substance.
Body weight:
Data for body weight at necropsy was not recorded.
Gross pathology:
No abnormalities were noted at necropsy.

Mortality:

 Dose:  sex:  1h  24h  48h  7 days  14 days
 5  ml/kg  male   0/5   0/5   0/5   0/5   0/5
 5 ml/kg  female   0/5   0/5   0/5   0/5   0/5
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the available data the tested substance has no concern for acute dermal toxicity. Since the active substance in the tested sample is only 17% the LD50 dermal calculated on the active substance is 850 mg/Kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
850 mg/kg bw
Quality of whole database:
The test is old and the summary lacking of many data.

Additional information

Only oral exposure pattern is covered by studies on the substance, while inhalation and dermal exposure are covered by tests on a similar substance. This similar substance is a metabolite, that from the point of view of dermal and pulmonary mucous absorption can be considered as a conservative example. The metabolite is in fact smaller, less hydrophylic and with a higher potential for adsorption and toxicity. In case of inhalatory toxicity the discriminating level for powder of 5 mg/L is reached, even if the study summary is quite poor, while for dermal toxicity the application was made with a mixture where the concentration of active ingredient was too low to have the study covering the endpoint by itself. Based on what has been agreed during the 15th Meeting of Competent Authorities for REACH and CLP (CARACAL),8 – 9 July 2014, considering the evidence presented as well as the comments by MS, the Commission services consider that an adaptation of point 8.5.3 of Annex VIII to REACH is justified in order to not require information on acute dermal toxicity for substances that have shown no toxicity in acute oral toxicity test up to the limit dose of 2000 mg/kg bw and no indications for systemic toxicity in other studies with dermal application (skin irritation or sensitisation studies) have been observed.

Testing the inhalation route is not appropriate since eposure is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Considering the overview of available studies it can be nevertheless concluded that the substance doesn't arise any concern for acute toxicity

Justification for selection of acute toxicity – oral endpoint

Several studies on acute toxicity have been performed on formulations containing the substance as active ingredient, even better reported studies than the key study, but none of them have been performed in order to guarantee that the concentration of pure active ingredient will be over 2000 mg/Kg bw; In Ramm W. (1986) study, the substance was tested at 5000 mg/Kg, and the active ingredient being the 72%, it can be considered valid for classification

Justification for selection of acute toxicity – inhalation endpoint

No study is available on the substance. A study has been performed on a similar substance, a similar possible metabolite, that from the point of view of pulmonary mucous absorption is a conservative example. The metabolite is in fact smaller, less hydrophylic and with a higher potential for adsorption and toxicity.

Justification for selection of acute toxicity – dermal endpoint

No study is available on the substance. A study has been performed on a similar substance,  a similar possible metabolite, that from the point of view of dermal absorption is  a conservative example. The metabolite is in fact smaller, less hydrophylic and with a higher potential for adsorption and toxicity.

Justification for classification or non-classification

Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table 3.1.1 of CLP Regulation. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE). The limit value that can trigger to Classification is 2000 mg/Kg both for oral exposure pattern and 5 mg/L for inhalation powder exposure. Having tests for both routes demonstrating no effects above 3600 mg/Kg bw for oral and 5.61 mg/L for inhalation

No classification for acute toxicity oral is warranted under Regulation 1272/2008

No classification for acute toxicity inhalation is warranted under Regulation 1272/2008