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Description of key information

Acute oral and dermal toxicity studies are available, performed similar to or according to OECD test guidelines respectively. The LD50 values are > 2000 mg/kg bw for both studies.

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:
02 December - 20 December, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed equivalent or similar to OECD 401 guideline. Limited information about substance identity and no GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(deleted in december 2002)
Deviations:
yes
Remarks:
Not all clinical examinations performed (body weight, necropsy), but considered not to have affected the outcome of the study.
GLP compliance:
no
Remarks:
performed before GLP was in place in the EU
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
- Source: Winkelman, D-4791 Borchen
- Age at study initiation: males: 56 days; females: 66 days
- Weight at study initiation: males: 144-166 g; females: 139-153 g
- Fasting period before study: 16 hours
- Housing: One animal per cage in Makrolon Type II cages
- Diet (e.g. ad libitum): standard diet (ALTROMIN®)
- Water: Free access to water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 50 - 60
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 237 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 21.5 mL/kg

Doses:
5110 mg/kg
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: Not indicated
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, mortality
Statistics:
Calculation LD50 determined with Probitanalyse (1952) (if required).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 110 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
In all animals diarrhoea was observed on the first day (day 1) after application.
Body weight:
No data.
Gross pathology:
No data
Other findings:
None.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with male and female rats, performed equivalent or similar to OECD 401 guideline, the LD50 was calculated to be >5110 mg/kg.
Executive summary:

In an acute oral toxicity study, performed comparable to OECD test guideline 401, male and female rats were exposed to 5110 mg/kg via gavage. No deaths occurred during the study. In all animals diarrhoea was observed on the first day (day 1) after application. The LD50 was determined to be >5110 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 110 mg/kg bw
Quality of whole database:
The study has been performed equivalent or similar to OECD 401 guideline. The report contains limited information about substance identity and was not conducted according to GLP principles.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
06SEP2012 to 20SEP2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 12 weeks old)
- Weight at study initiation: 319g -362g for males, 198g - 236g for females
- Housing: Group housing (acclimatization period) or individual housing (experimental period) in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimatization period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 06SEP2012 to 20SEP2012
Type of coverage:
occlusive
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and elastic bandage. A piece of tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg.

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE: water
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

Dose volume: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
None performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead on day 2 of treatment.
Clinical signs:
Chromodacryorrhoea and/or piloerection were noted in the majority of animals between days 1 and 3. Hunched posture was seen in one male on Day 1 and flat posture was seen in one male on day 1.
The animal found dead showed hunched posture, piloerection, chromodacryorrhoea and ptosis on day 1.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
Macroscopic post mortem examination of the animal that died during the study and of the animals surviving to the end of the study did not reveal any abnormalities.
Pelvic dilation of the kidneys (one male), is commonly noted among rats of this age and strain and were therefore considered not toxicologically significant.
Other findings:
Scales were seen in the treated skin-area of one animal during the observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guideline, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity test was performed according to OECD/EC guideline and GLP principles. Five male and five female rats were exposed to 2000 mg/kg bw for 24 hours. One female was found dead on day 2, this animal showed hunched posture, piloerection, chromodacryorrhoea and ptosis on day 1. In the majority of the other rats, clinical signs such as chromodacryorrhoea and/or piloerection were noted between days 1 and 3. Hunched posture was seen in one male on day 1 and flat posture was seen in one male on day 1. No changes in body weight gain were noted, no abnormalities were found after nacroscopical examination. Scales were seen in the treated skin-area of one animal during the observation period.

Based on these data, the test substance is not classified for acute dermal toxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Additional information

In an acute oral toxicity study, performed comparable to OECD test guideline 401, male and female rats were exposed to 5110 mg/kg via gavage. No deaths occurred during the study. In all animals diarrhoea was observed on the first day (day 1) after application. The LD50 was determined to be >5110 mg/kg.

An acute dermal toxicity test was performed according to OECD/EC guideline and GLP principles. Five male and five female rats were exposed to 2000 mg/kg bw for 24 hours. One female was found dead on day 2, this animal showed hunched posture, piloerection, chromodacryorrhoea and ptosis on day 1. In the majority of the other rats, clinical signs such as chromodacryorrhoea and/or piloerection were noted between days 1 and 3. Hunched posture was seen in one male on day 1 and flat posture was seen in one male on day 1. No changes in body weight gain were noted, no abnormalities were found after nacroscopical examination. Scales were seen in the treated skin-area of one animal during the observation period.


Justification for selection of acute toxicity – oral endpoint
One study is available with Klimisch reliability 2.

Justification for selection of acute toxicity – dermal endpoint
One study is available with Klimisch reliability 1.

Justification for classification or non-classification

Based on the available studies, sodium ferrocyanide is not classified for acute toxicity according to the CLP Regulation (No) EC 1272/2008.