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Key value for chemical safety assessment

Acute toxicity: via oral route

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Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The information on this study is in the form of a letter report. It was conducted prior to international guidelines and good laboratory practice standards. The study appears to be robust.
Principles of method if other than guideline:
Conducted generally as modern studies - a single gavage dose to six groups of rats with observation for 14 days followed by sacrifice with gross necropsies.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test material was administered as a 50% weight/volume suspension in water.
Doses:
0, 215, 464, 1000, 2150, 4640 and 10000 mg/kg bw
No. of animals per sex per dose:
5 M/dose
Control animals:
yes
Details on study design:
The test material was administered orally by stomach tube to 6 groups, each composed of 5 male albino rats (Dublin Sprague-Dawley strain, 201-291 g in weight). The test material was administered as a 50% weight/volume suspension in water. Food was withheld for approximately 18 hr prior to dosing. Food (commercial pellets) and water was then available ad libitum. The rats were housed in groups in wire mesh cages suspended above the droppings. All animals were observed closely for gross signs of systemic toxicity and mortality several times during the day of dosage, and at frequent intervals thereafter for a total of 14 days. At the end of the 14 d observation period, rats were weighed, sacrificed by cerebral concussion, and gross necropsies performed.

Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
None due to test article toxicity. One death at 464 mg/kg due to gavage error.
Clinical signs:
other: other: none
Gross pathology:
see remarks

One rat at the 464 mg/kg dose was found dead on the third experimental day. Necropsy findings indicated the death was due to gavage error (e.g. intratracheal). No other mortalities occurred during the 14-day observation. The oral LD50 was determined to be > 10000 mg/kg bw. The average body weight gain in each group was reported as within the normal limits for rats of the age, sex and strain employed in the study. At gross necropsy on termination, slight congestion of the kidney was observed in rats at the lower dose levels, and moderate to marked congestion of the kidneys were observed at the highest dose level. 

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: expert judgment
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed prior to establishment of GLPs.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals or test system and environmental conditions:
5M/5F
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
Single dose administered once: 10000 mg/kg bw; volume = 20 ml/Kg bw
No. of animals per sex per dose:
5 M/5F
Control animals:
no
Details on study design:
Single dose administered after a 4 hr fast. Observed during first 4 hr and daily thereafter for 14 d. Subjected to gross necropsy at end of 14 day observation.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
no animals died during the test.
Clinical signs:
other: other: no clinical signs were observed.
Gross pathology:
no gross lesions detected on necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 in mice was found to be > 10,000 mg/kg bw.
Executive summary:

The oral LD50 in mice was found to be > 10,000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
K2

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed prior to international gudielines and good laboratory practices. It used a micronized form of the commerical product. Micronization may impact (e.g. increase) the potential for toxicity.
Principles of method if other than guideline:
Rats were exposed to a single concentration of the test material for 4 hours and observed for 14 days afterward.
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and five female rats were used. The rats were housed by sex in groups of 5 in metal cages above the droppings in temperature and humnidity contolled quarters. Purina Laboratory Chow and water were available ad libitum.
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
"The group of 10 rats was placed in a sealed 59.1 liter glass chamber and exposed for 4 hours to a dynamic atmosphere containing the dust of the test material. In order to prevent "piling up" during the exposure, the rats were separated into 4 units of 2 or 3 rats each. Addition of the test compound to the test chamber atmosphere was controlled by a Wright Dust Feeder. Dried and filtered air was passed through the mechanism and directly into the exposure chamber. Airflow was regulated by means of a flowmeter (Gelman Insturment Company, Ann Arbor, Michigan, Model No. 8221). The calculated atmospheric concentration administered was approximately 10.92 mg/L* of FM PHT4 (micronized), Lot N0. 6332-B.
*The physical properties of the test compound precluded administration of the test material at a higher atmospheric concentration."
Duration of exposure:
4 h
Concentrations:
10.92 mg/L
No. of animals per sex per dose:
5M/5F
Control animals:
no
Details on study design:
The rats were observed continuously during and immediately after the 4 hr exposure. All rats which died on study were necropsied. All surviving animals were necropsied at the end of the 14 d observation period.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10.92 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None.
Clinical signs:
other: During exposure: decreased activity, eye squint, slight dyspnea, erythema. At 24 hr: 1 rat with nasal "porphyrin" discharge. At 10-14 days: several rats with diarrhea.
Body weight:
All rats exhibited normal body weight gain during the study.
Gross pathology:
No compound-related gross lesions were observed.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The 4 hr LC50 in rats was > 10.92 mg/L.





Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 000 mg/m³ air
Physical form:
inhalation: dust
Quality of whole database:
K2

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The information on this study is in the form of a letter report. It was conducted prior to international guidelines and good laboratory practice standards. The study appears to be robust.
Principles of method if other than guideline:
Conducted generally as modern studies - a single dermal dose to four groups of rabbits with observation for 15 days followed by sacrifice with gross necropsies.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
The animals were housed individually in metal cages elevated above the droppings. Food (Purina Rabbit Pellets) and water were available at all times.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The test material was applied to the skin of four groups of albino rabbits each (1344 – 2310 g). The test material was applied moistened with sufficient water to form a paste. The sample was applied to the intact abdominal skin area from which the fur had been removed with electric clippers. The sample was applied under a binder of rubber dental damming which was placed around the trunk of the animal. The trunk was wrapped securely with gauze and adhesive tape to keep the binder and test material in contact with the skin and to prevent ingestion. After 24 hr, the binders were removed and any unabsorbed material was removed by gentle sponging with a moistened towel.
Duration of exposure:
24 hr
Doses:
1000, 2150, 4640, 10000 mg/kg bw.
No. of animals per sex per dose:
4/dose
Control animals:
no
Details on study design:
The test material was applied to the skin of four groups of albino rabbits each (1344 – 2310 g). The test material was applied moistened with sufficient water to form a paste. The dosage levels were 1000, 2150, 4640, 10000 mg/kg bw. The sample was applied to the intact abdominal skin area from which the fur had been removed with electric clippers. The sample was applied under a binder of rubber dental damming which was placed around the trunk of the animal. The trunk was wrapped securely with gauze and adhesive tape to keep the binder and test material in contact with the skin and to prevent ingestion. After 24 hr, the binders were removed and any unabsorbed material was removed by gentle sponging with a moistened towel. The rabbits were observed for gross signs of systemic toxicity at several intervals during the day of application and for gross signs of dermal irritation and systemic toxicity daily thereafter for a total of 15 days. A gross necropsy was performed on animals dieing on-test. At the end of the 15-d observation, all rabbits were weighed, sacrificed by air embolism, and a gross necropsy performed.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
None due to test article. Four rabbits died from enteritis. See remarks.
Clinical signs:
other: other: Rabbits at the highest dose level appeared depressed after application of test material. Thereafter, these animals appeared normal. Rabbits at the 3 lower doses showed no clinical signs during dosing. No skin irritation was observed at removal o
Gross pathology:
Gross necropies on the four animals that died on test were hampered by autolytic changes. Gross necropsies at scheduled sacrifice showed no gross lesions.

Four rabbits died between the 10th and 13thday of the study: 1 in the 1000 and 4640 mg/kg groups and 2 in the 2150 mg/kg group. Death was preceded by body weight loss and diarrhea, and attributed to enteritis, a common syndrome in laboratory rabbits. There were no other mortalities. The LD50 was determined to be > 10000 mg/kg bw.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
K2

Additional information

The oral LD50 in rats and mice was > 10000 mg/kg bw. The dermal LD50 in rabbits was > 10000 mg/kg bw. The inhalation LC50 was > 10.92 mg/L.

Justification for classification or non-classification

The substance was not acutely toxic by the oral, dermal or inhalation routes.


Based on the available study data classification is not required in accordance with Regulation 1272/2008 (CLP)