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Description of key information

Three acute toxicity studies were conducted on HFP Kinetic Dimer.  The results of the studies are: 
Acute Inhalation in Rats: 4-hour LC50 > 21.69 mg/L when tested according to OECD 403 (1981).
Acute Inhalation in Mice: 4-hour LC50 between 2.20 mg/L (LC0) and 15.58 mg/L (LC100).
5-Day Oral Toxicity in Rats: LD50 > 450 mg/kg-day and < 1000 mg/kg-day.

Key value for chemical safety assessment

Additional information

To evaluate the acute inhalation toxicity of the test article (liquid, purity >93%, molecular weight 300 g/mol, vapor pressure 235 mmHg at 25 C, Batch No. L12596), the test material was administered to Wistar rats for a single continuous 4-hour period. The study was performed under OECD GLP (1992) conditions. The study method was based on OECD Guideline 403 (1981) and EC Directive 92/69/EEC, Part B.2 (1992). Rats (5/sex) were exposed by nose-only to 21.69 +/- 1.084 mg/L (vapor) MTDID 948, dissolved in n-hexane, for 4 hours. Following exposure, the animals were observed for 14 days. After the observation period, the animals were anesthetized by i.p. injection of sodium pentobarbital (at least 320 mg/kg-bw) and were euthanized by exsanguination. Body weights and clinical observations were recorded. Gross necropsies were performed. During the exposure period, no clinical signs were detected in any animals. One male and one female were found dead on test day 4. On test day 4, the following clinical signs were observed in the surviving animals: tachypnea (1 male/3 females), hunched posture (0/1), ruffled fur (2/1) frightened behavior (1/0), and tremor (1/0). On test day 5, one male and one female were found dead. The remaining animals had returned to normal on test day 5. No clinical signs were detected in the remainder of the observation period. All surviving animals gained weight consistently during the observation period, with the exception of one male and one female, which lost weight during the first week post exposure but regained weight to exceed their pre-exposure weight during the second week post exposure. Macroscopic findings were only detected in the animals that died during the observation period. The findings were: lungs incompletely collapsed, dark red discoloration (2 males/2 females); cannibalism, larynx, tongue, and thyroid gland, missing (0 males/1 female). Based on the results of this study, the 4-hour rat inhalation LC50 of the test article is greater than 21.69 mg/L (vapor).

 

The acute inhalation toxicity of the test article (liquid, administered as a vapor, vapor pressure 235 mmHg at 25 C) was evaluated in male CD-1 mice. The study was not intended to comply with GLP standards. One mouse was exposed whole body, to 5078 ppm (62.3 mg/L) of the test article for one hour. A second group of 3 male mice were exposed whole body to 2539 ppm test article (31.15 mg/L) for one hour. A third group of 3 male mice were exposed whole body to 508 ppm test article (6.23 mg/L) for 30 minutes. For each exposure group, there was a group of air-exposed control animals. After the exposure period, all animals were observed for clinical signs of toxicity for a 14 day recovery period and then were euthanized via CO2 asphyxiation. Body weights and clinical observations of toxicity were recorded over the in-life phase of the study. Gross histopathological examinations were performed at the time of death or at the scheduled necropsy. The male mouse exposed to 62.3 mg/L demonstrated light shortness of breath 45 minutes into the exposure. The following day, this animal was observed to have CNS depression, ataxia and was unable to reach for food. The animal was euthanized “in extremis” and necropsied immediately. Mottled pink lungs were observed during gross necropsy. During the 31.15 mg/L exposure all mice appeared to have slight labored/rapid breathing during last 10 minutes of exposure period and weight loss was noted during the immediate days following test article exposure. On day 6 post-exposure, all animals exposed to 31.15 mg/L were found dead. Gross necropsy revealed dark reddened lungs, minimal abdominal fat, and empty gastrointestinal tracts. All mice appeared normal throughout the 30-minute, 6.23 mg/L exposure period and no weight losses were noted in the exposed animals. Reddened lungs observed at the time of necropsy were attributed to CO2 euthanasia since this was also observed in the air-exposed control animals. Based on the results of the study, the LC50 of the test article is between 6.23 mg/L (30 min) and 31.15 mg/L (vapor) (1 hour), which is equivalent to 4-hour exposures of 2.20 mg/L and 15.58 mg/L.

 

The oral toxicity of the test article was (clear, colorless liquid; CASRN 84650-68-0, purity 98.5%; Lot 4, with spikes) was evaluated in Wistar rats in order to determine appropriate doses for a 28-day subacute study. This study was performed under OECD GLP (1997) conditions. Female rats (3/group) received 150, 450, or 1000 mg/kg-day of the test article by oral gavage for 5 days. After the last dose, all surviving animals were euthanized, and macroscopic examinations were performed. Body weights and clinical observations were recorded. Kidney and liver weights were recorded. 1000 mg/kg-day: All rats were euthanized between days 2 and 4 due to moribund condition. The following clinical observations were noted in all rats: lethargy, flat/hunched posture, abnormal gait, labored respiration, piloerection, diarrhea, brown staining of genital region, pale, hypothermia, and/or abdominal swelling. Macroscopic examination revealed: gastrointestinal tract distended with gas (all animals), reduced size of the spleen and thymus (2 animals), thickened and pale discolored liver with accentuated lobular pattern (1 animal), and enlarged adrenal glands (1 animal). 450 mg/kg-day: All animals survived. Reduced food consumption was observed, and all animals lost up to 21% of their body weights. The following clinical observations were noted in all rats: lethargy, hunched posture, piloerection, diarrhea, brown staining of genital region, lean appearance, and abdominal swelling (1 animal). Macroscopic examination revealed: gastrointestinal tract distended with gas (all animals) and reduced size of the spleen and/or thymus (2 animals). One animal had a slightly lower liver weight. Other liver and kidney weights were normal. 150 mg/kg-day: All animals survived. Reduced food consumption was observed, and all animals lost up to 20% of their body weights. The following clinical observations were noted in all rats: hunched posture, piloerection, and diarrhea. Macroscopic examination revealed: gastrointestinal tract distended with gas (all animals), red discoloration of mesenteric lymph nodes (1 animal), and reduced size of the spleen (1 animal). Liver and kidney weights were normal. The 5-day oral LD50 of the test article is greater than 450 mg/kg-day but less than 1000 mg/kg-day.

Justification for classification or non-classification

HFP Kinetic Dimer meets the CLP criteria for classification as Acute Tox. 4 (oral).