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Administrative data

Description of key information

No lethality was observed following acute exposure to either n-butyl-3-hydroxybutyrate or the related ester alcohol, isopropyl-3-hydroxybutyrate, by either oral, dermal or inhalation.  Dosages were administered up to a limiting concentration of 5000 mg/kg via oral or dermal administration, and up to 5.11 mg/L (mist/aerosol) via inhalation exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
An acute oral toxicity test was conducted with rats to determine the potential for n-butyl-3-hydroxybutyrate to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 5,000 mg/kg of body weight in female rats. ' An initial limit dose of 5,000 mglkg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, two additional females received the same dose level, simultaneously. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice. All animals survived test substance administration, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Justification for selection of acute toxicity – inhalation endpoint
An acute inhalation toxicity test was conducted with rats to determine the potential for Isopropyl-3-hydroxybutyrate (IPHB) to produce toxicity from a single exposure via the inhalation (nose-only exposure) route. Data for IPHB was utilized in a read-across fashion, as a reasonable surrogate for effects that are likely to result from exposure to n-butyl-3-hydroxybutyrate. Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance as a mist is greater than 5.11 mg/L in male and female rats. After establishing the desired generation procedures during pre-test trials, ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test substance were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded prior to exposure and again on Days 1, 3, 7, and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. The gravimetric chamber concentration was 5.11 mg/L. The mass median aerodynamic diameter was calculated to be 2.26 11m based on graphic analysis of the particle size distribution as measured with an ACFM Andersen Ambient Particle Sizing Sampler.
All animals survived exposure to the test atmosphere. Following exposure, all rats exhibited irregular respiration. However, they recovered by Day 4 and appeared active and healthy for the remainder of the observation period. Although all animals lost body weight on Day 1, they showed continued weights gain thereafter and gained weight through Day 14. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Justification for selection of acute toxicity – dermal endpoint
An acute dermal toxicity test was conducted with rats to determine the potential for Isopropyl-3- hydroxybutyrate (IPHB) to produce toxicity from a single topical application. Data for IPHB was utilized in a read-across fashion, as a reasonable surrogate for effects that are likely to result from exposure to n-butyl-3-hydroxybutyrate. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 5,000 mg/kg of body weight in male and female rats. Five thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived exposure to the test substance and gained body weight during the study. Other than the dermal irritation noted at six dose sites between Days 1 and 2, there were no other clinical findings recorded for any animal over the course of the study. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Justification for classification or non-classification

No lethality was observed following acute exposure to either n-butyl-3-hydroxybutyrate or the related ester alcohol, isopropyl-3-hydroxybutyrate, by either oral, dermal or inhalation. Dosages were administered up to a limiting concentration of 5000 mg/kg via oral or dermal administration, and up to 5.11 mg/L (mist/aerosol) via inhalation exposure.

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