Registration Dossier

Administrative data

Description of key information

Oral toxicity
Albert & Kincke (1982): An acute oral toxicity study was conducted in the rat on Crude Catalyst 32899. Five dosage levels (0, 560, 1000, 1800, and 3600 mg/kg) were tested in groups of ten (5 male and 5 female) fasted rats. The acute oral LD50 was calculated to be 850 mg Crude Catalyst 32899/kg body weight with 95% confidence limits of 612-1114 mg/kg.
Thorpe (1981): The acute oral LD50 value of 32899 in rats (administered as a 50% (m/m) aqueous suspension concentrate) was 1,426 mg/kg with 95% fiducial limits 1,085-1,772 mg/kg.
Rats which survive doses of 2,160 mg/kg or more develop severe peripheral neuropathy within approximately one week of dosing. There are indications that animals surviving doses of 1,350 mg/kg have minor degenerative changes in peripheral nerve but do not develop clinical signs of neuropathy.
Dermal toxicity
Albert, Wilborn & Wimberley (1982): The test results indicate the LD50 of the test material is in excess of 2000 mg/kg. Based on these results the test material would not be considered as having a skin irritant effect.
Inhalation toxicity
Beatty (1980): The four-hour inhalation LC50 of catalyst 32899 was estimated to be 3 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
850 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Four studies have been carried out to assess for acute toxicity to the test material, two oral (Albert & Kincke, 1982; Thorpe, (1981)); one dermal (Albert, Wilborn & Wimberley, 1982) and one inhalation (Beatty, 1980).

All studies were evaluated for suitability, based on this evaluation, it was established that the studies were neither GLP compliant or conducted according to standard guidelines. Despite this, they were considered to be acceptable for the purposes of classification and labelling and assigned a Klimisch rating of 2.

Oral Toxicity

Albert & Kincke (1982)

An acute oral toxicity study was conducted in the rat on Crude Catalyst 32899. Five dosage levels (0, 560, 1000, 1800, and 3600 mg/kg) were tested in groups of ten (5 male and 5 female) fasted rats. The acute oral LD50 was calculated to be 850 mg Crude Catalyst 32899/kg body weight with 95% confidence limits of 612-1114 mg/kg. Lethalities generally occurred within 24 hours after dosing. The onset of clinical signs of toxicity occurred within one hour. Survivors generally recovered from observable clinical signs of toxicity within 48 hours after dosing. Body weight gain of survivors was decreased in the 560 mg/kg female dosage group at days 7 and 14. Prominent clinical signs of toxicity included: polyuria, lacrimation, loss of pain reflex, ataxia, hypoactivity, emprosthotonus, diminished myotactic placing reflex, loss of righting reflex, clonic convulsions, and prostration. Necropsy findings in animals dying over the first 24 hours involved primarily the gastro-intestinal tract (distension with fluid and hemorrhagic areas in the stomach). Necropsy findings in survivors were not remarkable.

Thorpe (1981)

The acute oral LD50 value of 32899 in rats (administered as a 50% (m/m) aqueous suspension concentrate) was 1,426 mg/kg with 95% fiducial limits 1,085-1,772 mg/kg. Rats which survived doses of 2,160 mg/kg or more developed severe peripheral neuropathy within approximately one week of dosing. Rats which survived doses of less than 2.160 mg/kg did not develop clinical signs of neuropathy although small enzyme increases consistent with very slight degenerative changes were seen in some animals dosed with 1,350 mg/kg.

Dermal Toxicity

Albert, Wilborn & Wimberley (1982)

An acute dermal toxicity study was conducted in the rabbit on Crude catalyst 32899 (WRC Tox. Sample No. 14200-124-1E). The 2000 mg/kg dose of the test material was applied as a 50% paste, prepared using 0.9% normal saline under an occlusive wrapping to intact or abraded skin sites of 8 male and 6 female rabbits. Seven male and five female rabbits were used as controls. Skin irritation effects observed in the test animals following removal of the wrappings at 24 hours were comparable to controls. No skin irritant effects were evident at 14 days. No treatment-related Clinical signs of toxicity occurred in the study. One lethality (1/14) occurred in the test group on day 12. Clinical signs observed in the rabbit that died included a lack of appetite and hypoactivity, diarrhea and/or no observable feces for four days prior to death. Necropsy of this rabbit was not remarkable because of generalized autolysis. Necropsy of surviving rabbits was not remarkable and included only incidental effects not related to treatment. The test results indicate the LD50 of the test material is in excess of 2000 mg/kg.

Inhalation toxicity

Beatty (1980)

In order to determine the inhalation LC50 groups of male and female Fischer 344 rats underwent single, four hour exposures to 32899 dust at concentrations of 1.6 and 5.8 mg/L. Exposures were performed in a 220 L head only chamber. Paticle size distribution and both nominal and actual concentrations of 32899 dust were determined. After exposure the animals were observed for fourteen days and underwent gross necropsy soon after death or upon sacrifice at the end of the observation period. Gross pathology findings which were observed only in the 5.8 mg/L exposure groups were insufficient to explain the observed deaths. As a result of this study the four-hour inhalation LC50 of catalyst 32899 was estimated to be 3 mg/L.

Justification for classification or non-classification

The study carried out by Albert and Kincke was the more recent study of the two oral toxicity studies and also provided a lower LD50 estimate figure of 850 mg/kg/day. Based on this information, this study was considered to be the study of interest for the purposes of classification and labelling and allocated as the key study for assessment of acute oral toxicity.

Under classification and labelling guidelines a test material can be considered to be classified as Category 4 for Acute oral toxicity when results indicate an acute toxicity estimate between 300 and 2000 mg/kg/bw.

Based on this information the test material is considered to be classified as Category 4 for Acute toxicity by the oral route according to Regulation (EC) No 1273/2008.

Under classification and labelling guidelines a test material can be considered to be classified as hazardous for Acute dermal toxicity when results indicate an acute toxicity estimate of less than 2000 mg/kg/bw.

Based on this information the test material is not considered to be classified as hazardous for Acute toxicity by the dermal route according to Regulation (EC) No 1273/2008.

Under classification and labelling guidelines a test material can be considered to be classified as Category 4 for Acute inhalation toxicity when results indicate an acute toxicity estimate between 1.0 and 5.0 mg/L.

Based on this information the test material is considered to be classified as Category 4 for Acute toxicity by the inhalation route according to Regulation (EC) No 1273/2008.