Registration Dossier

Administrative data

Description of key information

Acute toxicity studies are available for Fe-EDTA and Na-glucoheptonate

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
July 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed study under GLP
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
see section 13
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD/Crl: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chalrles River, Germany
- Age at study initiation: 7 weeks
- Weight at study initiation: 177-183 g
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 55 +/-5%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 11 To:26th July 2007
Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous hydroxypropylmethylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage):10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
no
Statistics:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No mortalities.
Mortality:
no mortalities
Clinical signs:
no clinical signs
Body weight:
Animals gained the expected body weight
Gross pathology:
No pathologicla changes observed
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
LD50 exceeding the limit dose of 2000 mg/kg bw
Executive summary:

In an acute oral toxicity study according to OECD guideline 423 a group of female CD rats received a limit dose of 2000 mg/kd bw of FeNaEDTA by gavage administration. No adverse effects were noted, no clinical signs, no mortalities, no effect on body weight and no adverse findings at final necropsy after a 14 days observation period. The LD50 (oral,rat) exceeded 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Well performed GLP studies available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP; one remark: 44% of the particles was smaller than 4 micron, indicating that the MMAD was slightly above 4 micron (1-4 micron is required)
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See section 13
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 51 days(males), 65 days (females)
- Weight at study initiation: 214 - 250 g
- Fasting period before study: 24 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 55 +/-15%
- Photoperiod (hrs dark / hrs light): 12/12 hours
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: water
Details on inhalation exposure:
As no dust aerosol could be generated, the test item was dissolved in water to a 5.7% solution the approximate limit of solubility.This solution was used to generate the aerosol of nominal 55.56 mg/L air.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal concentration: 55.56 mg/L air
actual concentraion 2.75 +/- 0.19 mg/L air
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: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not required
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.75 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: +/- 0.19, No mortalities.
Mortality:
none
Clinical signs:
none
Body weight:
All animals gained the expected body weight.
Gross pathology:
No pathological findings

nominal concentration

actual concentration

mass median aerodynamic diameter

respirable amount particle size

≤4 µm

respirable amount particle size

≤4 µm

[µL/L air]

[mg/L air]

[µm]

[mg/L air]

[%]

55.56

2.75

2.730

1.21

44.1

Interpretation of results:
other: No classification needed
Remarks:
Migrated information
Conclusions:
LC50 (rat, 4h) exceeded 2.75 +/- 0.19 mg/L the maximum attainable concentration
Executive summary:

In an acute inhalation toxicity study according to OECD guideline 403 a group of 5 rats per sex was exposed to an aerosol concentration of 2.75 +/-0.19 mg/L air for 4h by the inhalation route. No adverse effects were noted, no clinical signs, no effects on body weight and no adverse findings at final necropsy after a 14 days observation period. It was noted that the MMAD was slight above 4 micron whereas 1 -4 micron is required.

The LC50(rat, dermal) exceeded 2.75 +/- 0.19 mg/L air.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Well performed GLP study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
July 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See section 13
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Germanz
- Age at study initiation: 51 days(males), 65 days(femalse)
- Weight at study initiation: 207 - 253 g
- Fasting period before study: 24 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2 °C
- Humidity (%): 55+/-5% r.H.
- Photoperiod (hrs dark / hrs light): 12/12 hours


IN-LIFE DATES: From: 11 To:25 July 2007
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x6 cm²
- Type of wrap if used: gauze, plastic sheet secured with adhesive


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure:24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):10 mL/kg bw
- Concentration (if solution): 0.2 mg/mL
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Statistics:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No mortalities.
Mortality:
none
Clinical signs:
none
Body weight:
no adverse effect
Gross pathology:
no adverse findings
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
LD50 (dermal, rat) exceeds 2000 mg/kg bw
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 a group of 5 rats per sex were administered a limit dose of 2000 mg/kg bw by the dermal route for 24h. No adverse effects were noted, no clinical signs, no effects on body weight, no local signs and no adverse findings at final necropsy after a 14 days observation period.

The LD50 (rat, dermal) exceeded 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Well performed GLP studies available

Additional information

Justification for classification or non-classification

As no acute toxicity was observed for the read across substances Fe-EDTA and Na-glucoheptonate, no GHS classification needed for acute toxicity.