Pentane-2,4-dione

Endpoint summary

Description of key information

LD50, oral, rat: 570 mg/kg bw (female); 760 mg/kg bw (male)
LD50, dermal, rabbit: 790 mg/kg bw (female) and 1370 mg/kg bw (male)
LC50, inhalation, rat: 5104 mg/m3

Additional information

Acute toxicity, oral, rat:

One study is available for assessment of acute toxicity by oral route (BRRC 48-34, 1985). Five male and five female Hilltop-Wistar rats per group were dosed with 0.25, 0.50, 0.71 and 1.00 mL/kg bw, equivalent to 243, 485, 689 and 970 mg test substance/kg bw by gavage. 5/5 males and 5/5 females died in the 1.00 mL/kg dose group and 1/5 males and 5/5 females in the 0.71 mL/kg dose group. No mortality occurred in the low dose groups. Most deaths occurred within 5 hours after administration. Signs of toxicity at 0.50 mL/kg and higher doses included sluggishness, tremors, kyphosis, lacrimation, unsteady gait, comatose appearance and prostration. At necropsy, findings included few remarkable lesions except enlarged cervical lymph nodes in most animals, suggesting the presence of a minor infection. An LD50 of 570 (female) and 760 (male) mg/kg bw was observed.

Acute toxicity, dermal, rabbit:

A study is availabe where undiluted 2,4-pentanedione (485, 970, 1940, 4850, 9700 mg/kg bw) was applied on the shaved dorsal skin (25 cm2) of 3-5 male or female New Zealand White rabbits/group for 24 h under occlusive conditions (BRRC 48 -34, 1985). No animal died within the lowest dose group, but 1/5 males and 4/5 females died in the 970 mg/kg bw dose group, 4/5 males and 5/5 females in the 1940 mg/kg bw dose group and all males in the two highest dose groups. Death occurred within 1-24 h after application. Signs of toxicity at 970 mg/kg bw or more were: dilated pupils, salivation. After dosing with 9700 mg/kg bw convulsions, local erythema, edema and necrosis (persisted for 1-7 d) and scab formation at day 14 were observed. Dead animals showed red mottled lungs, patchy congestion of tracheal mucosa, and a few stomachs with superficial black foci at necropsy. An LD50 of 790 (female) and 1370 (male) mg/kg bw was observed.

Acute toxicity, inhalation, rat:

Two studies are available where the acute toxicity after inhalation of test substance was investigated. In the key study Hilltop-Wistar albino rats (5 per sex and dose) were exposed for 4 hours to vapors of 2619, 3823, 5133 and 6288 mg test substance/m3 (Ballantyne, 1986). Deaths were observed within both male and female rats exposed to concentrations of 5133 and 6288 mg/m3 (mortality 8/10 and 6/10). Deaths occurred mostly during exposure or within 24 hours post-exposure (1 exception on day 3 in male rats in the 6288 mg/m3 group). No mortalities were observed with rats exposed to both low doses. Clinical signs observed in rats of the 2 high dose exposure groups included periocular, perinasal and perioral wetness and encrustation, forced respiration, distended abdomen, tremors, ataxia, decreased motor activity, a negative tail and toe pinch reflex and a slow righting reflex. The respiratory difficulties decreased motor activity and ataxia persisted in survivors through postexposure day 2. No clinical signs were observed in survivors of the 2 high dose exposure groups on day 6 and 5. The only clinical signs in the 3823 mg/m3 group were periocular wetness and decreased motor activity in both sexes of rats during exposure. These rats appeared normal again on postexposure day one. In the low dose group, no signs of toxicity were observable during or postexposure. In the rats that died, necropsy revealed red lungs, dark livers, gas-filled stomachs. No effects on sacrificed survivors were observed. The LC50 was 5104 mg/m3 (Ballantyne, 1986).

In a supporting study (GLP) two groups of 10 male and 10 female Fischer 344 rats were exposed to nominal 1225 or 1800 ppm (corresponding to 5108 and 7506 mg/m3) of the test substance in a 4 h exposure (Garman, 1995). 2/20 (1 male and 1 female) rats died immediately following 1225 ppm exposure and 6 males and 8 females died during or within 5 hours following the 1800 ppm exposure; clinical signs were blepharospasm, lacrimation, abdominal breathing, urogenital wetness, decreased activity, encrustation around eyes and nose.

Acute toxicity, intraperitoneal, mouse:

Additional information was received from an acute toxicity study (GLP) in mice after intraperitoneal injection of 579, 694, 833, 1000 and 1200 mg test substance/kg bw. All animals administered the 1200 mg/kg dose died within 4 hours after injection. The dose of 1000 mg/kg bw produced 80 % and 60 % mortality incidence and 833 mg/kg produced 60 % and 100 % mortality incidence in male and female mice, respectively. The lowest dose to produce mortality was the 694 mg/kg bw dose level which produced 20 % mortality in the male and female mice. An LD50 of 808 mg/kg bw was deduced.

In conclusion, the test substance has shown moderate toxicity after administration by oral, dermal and inhalation route.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

- Classification required for acute toxicity: Xn, R20/21/22

  

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008 (last amended by EC/286/2008 (2011-03-10)):

- Oral route: Category 4

- Dermal route. Category 3 (females), Category 4 (males)

- Inhalation route: Category 3