Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 440 mg/kg bw in rats.

Acute dermal toxicity: > 2000 mg/kg bw in rabbits

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:
Feb 1992-July 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP
Qualifier:
equivalent or similar to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Principles of method if other than guideline:
US 40 CFR 798, subpart A, standard Acute Oral Toxicity Method, similar to OECD 420.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Lot 11202AB, brownish white flaked solid, 116 g/100 ml solubility in water
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Healthy, young adult, outbred Sprague-Dawley albino rats were used in the study.
Animals were purchased from a registered commerical breeding laboratory (Charles River Laboratories, Wilmington, MA) and quarantined for 6 days.

Animals were group housed in polycarbonate cages
Hardwood chips were used as contact bedding.
Animal rooms were maintained at 68±3 °F, with a relative humidity at 30-70% with a minimum of 10 to 13 complete air exchanges per hour
12 hour light/dark cycles with full spectrum flourescent lights were used.

Animals were supplied with a commercial rodent ration (Agway Prolab, Waverly, NY) and municipal tap water ad libitum.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
After overnight fasting, animals were administered a single dose of the test substance by intragastric intubation, a ball tip gavaging needle and a syringe.
All animals were dosed within a 24 hour period.
Doses:
Dose levels of 4.0, 2.0, 1.0, 0.6, and 0.3 g/kg were selected for the range finding trial; 2 animals at each dose
Dose levels of 0.8, 0.5, and 0.2 g/kg were selected for the LD50 trial based on the results of the Range Finding Trial
No. of animals per sex per dose:
10 animals were used with each unique dose.in the main study
Control animals:
no
Details on study design:
Clinical observations were conducted daily for 14 days.
Any animal found dead was necropsied as soon as possible, but in no case later than 12 hours.
A gross necropsy was performed on all animals whether found dead or sacrificed at the end of the study at day 14.
Preliminary study:
8 of 10 animals died during the initial 4 hour observation period. The 2 animals in lowest dose (0.3 g/kg bw) survived. Gross necropsy of deceased animals showed hemorrhaging in the stomach and small intestine. No leasions were seen in the surviving animals.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
440 mg/kg bw
Based on:
test mat.
Mortality:
All animals at 0.50 g/kg bw and above died before the end of the study.
Clinical signs:
At 0.8 g/kg, alll animals showed signs of cyanosis during the initial 4 hour observation period before succumbing to death. Surviving animals at the 0.5 g/kg dose showed catalepsy and temors during the first 4 hours; 9 of 10 animals died. At the 0.2 g/kg dose, no toxicity was seen during the observation period.
Body weight:
Surviving animals gained body weight during the course of the study.
Gross pathology:
Gross pathologies of animals that died showed hemorrhaging in the stomach and small intestine.
Discoloration of the kidneys were also found in the animals which died during the observation period.

The LD50 of the test material in rats was found to be around 0.44 g/kg bw.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline acute oral toxicity study in CD rats, the LD50 of the test material was found to be 0.44 g/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
440 mg/kg bw
Quality of whole database:
adequate

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:
Feb-July, 992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP
Qualifier:
equivalent or similar to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Brownish white flaked solid, Lot # 11202AB
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Ten healthy young adult New Zealand White rabbits, five of each sex, were used in the study.
Animals were purchased from a registered commercial breeding laboratory (Eastern Rabbit Breeding laboratory, Taunton, MA)
Animals were in the weight range between 2.0 and 3.0 kilograms at the start of the study
Animals were 10-12 weeks old at the start of the study. They were quarantined for 5 days prior to the study.

Animals were all housed individually using suspended stainless steel cages marked with the corresponding animal number.
Hardwood Sani-chips were used as non-contact bedding under the cages.
Animal rooms were maintained at 68±F at 30-70% Humidity
A minimum of 10-13 complete air exchanges per house occured
12 hour light/dark cycles using full spectrum fluorescent lights were used.

Animals were supplied with a commercial rabbit ration (Agway Prolab, Waverly, NY) and municipal tap water ad libitum.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Animals were weighed prior to testing and their fur clipped 24 h prior to adminstration of test material. The test substance was introduced under gauze patches two single layers thick and applied directly to the skin of the body surface (approximately 10%) of each of the ten animals. Animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandaging.
Duration of exposure:
24 hours
Doses:
2 g/kg
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
After the exposure period, the wrapping was removed from the animals and the site rinsed gentily with USP water to remove remaining test material. Any skin lesions found were graded 30-60 minutes after bandage removal. Animals were observed for erythema and edema for a 24 h observation period. The animals were observed daily for 14 days. Any animal found dead was necropsied within 12 hours. All animals underwent a gross necropsy. Surviving animals were euthanised with an injectable barbiturate, Euthanasia-5 (Veterinary Laboratories Inc, Lenexa , KS, USA).
Statistics:
none
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
given as > 2 g/kg
Mortality:
No animals died during the 14 day observation period
Clinical signs:
There were no overt signs of toxicity exclusive of skin irritation noted in any test animal during the observation period. There was no evidence the animals experienced pain or suffering
Body weight:
All animals gained weight when assessed at 14 days post exposure. Four animals lost weight during the first 7 days but regained weight by day 14
Gross pathology:
Necrosis was observed in the skin in all animals. Gross necropsy showed that necrosis penetrated through the skin into the underlying muscle. It also showed atrophy of the spleen and discoloration of the liver and kidneys.

LD50 > 2 g/kg bw.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is considered nontoxic in rabbits at a dose of 2000 mg/kg bw for 24 h, occlusive exposure, based upon the absense of mortality in a 14 day limit dose acute dermal toxicity study. Necrosis of the skin was observed in all animals at necropsy but no other clinical signs were reported.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
adequate

Additional information

The acute oral toxicity LD50 is calculated to be 440 mg/kg bw in rats. The acute dermal toxicity LD50 is greater than 2000 mg/kg bw. It is noted that all animals in the dermal study displayed signs of skin necrosis after a 24 h occlusive exposure to the test material in intact skin.

Justification for classification or non-classification

The test substance shows an acute oral LD50 of 440 mg/kg bw, which falls into GHS category 4 (300 mg/kg bw < LD50 < 2000 mg/kg bw), according to Regulation EC No. 1272/2008. The substance is not classified for acute dermal toxicity, as the LD50 exceeds 2000 mg/kg bw in rabbits.