Butyraldehyde

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

10

Dose descriptor:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

30 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

5

Dose descriptor starting point:

NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Additional information - workers

Summary/overview of the toxicity of n-butanal

 

Toxicokinetics

 

An adequate assessment of the basic toxicokinetics of n-butanal can be made from the existing toxicity data and theoretical considerations, without the need for specific testing. Extensive oral absorption is predicted based on the substance molecular size, solubility, chemical structure and on the basis of experience with other related aldehyde compounds. The molecule additionally satisifies Lipinski's rule of 5 (OECD QSAR Toolbox). Absorption following inhalation exposure is also likely to be extensive. Dermal absorption is likely to be extensive as evidenced by the results of the acute dermal toxicity studies. Rapid and extensive distribution can be predicted based on the knowledge of related compounds. N-butanal is a structurally simple organic substance and its mammalian metabolism can be readily predicted using knowledge of the metabolism of other simple aldehydes. Oxidative metabolism of the terminal aldehyde group by cytochrome P450 and other enzymes to form the corresponding acid, butanoic (butyric) acid, is predicted. Rapid and extensive renal excretion of n-butanal and its metabolite butanoic acid is predicted, based on their water solubility. Bioaccumulation is considered to be unlikely.

 

Acute toxicity

 

A large number of toxicity studies are available in various species. The results indicate that the substance is of relatively low toxicity. Acute oral toxicity studies report LD50 values in the range 2490 -5900 mg/kg bw. Acute dermal toxicity studies report LD50 values in the range 1020 ->5000 mg/kg bw. Acute inhalation studies report LC50 values in the range >5.4 -49 mg/L in the rat. A study in the mouse reports an intraperitoneal LD50 value of 1140 mg/kg bw.

 

Irritation / corrosion

 

The results of skin irritation studies are conflicting, in part due to the use of abraded skin in older studies. The various studies available are of different design and report varying degrees of skin irritation. The results of the most reliable study (Hoechst, 1988) indicate that the substance does not require classification as a skin irritant. The results of eye irritation studies indicate that the substance requires classification as an eye irritant.

 

Sensitisation

 

The results of a Buehler study show a 0% response to challenge with 10% n-butanal and a 10% response to challenge with 25% n-butanal, following induction using 50% n-butanal. The results indicate a weak sensitisation potential and are not sufficient to trigger classification of the substance as a sensitiser.

 

Repeated dose toxicity

 

A number of studies are available using oral exposure and inhalation exposure. Repeated dose oral toxicity studies do not show any evidence of systemic toxicity, but show local effects (irritation) of the gastric mucosa at all dose levels in a 90 -day rat study; an overall LOAEL of 75 mg/kg bw/d is derived. Repeated dose inhalation studies are notable for the absence of any signs of systemic toxicity; an overall NOAEC of 150 mg/m3 is derived for local effects from a sub-chronic rat inhalation toxicity study.

 

Genetic toxicity

 

No evidence of genetic toxicity was seen in a number of Ames tests. Positive results are reported in studies in vitro for mammalian cell mutation and clastogenicity. Positive findings are reported in a study of sperm cytogenetics in the mouse, however the reliability of this study is considered to be limited. Negative results are reported in high quality (NTP) mouse micronucleus and Drosophila SLRL assays.

 

Reproductive toxicity

 

No evidence of reprodcutive toxicity was seen in a one-generation study with the read-across substance propionaldehyde at inhalation concentrations of up to 1500 ppm (3560 mg/m3). No effects on sperm parameters were seen in a 13 -week study in rats and mice performed with isobutyraldehyde at concentrations of up to 2000 ppm (5890 mg/m3).

 

DNEL derivation

 

The substance does not show any effects of concern, with the exception of local irritation at the site of contact. These effects are therefore relevant to the derivation of DNEL values.

 

Systemic effects (dermal)

 

There are no repeated dose dermal toxicity studies; there is no evidence of systemic toxicity from repeated dose oral and inhalation toxicity studies. Very high dose levels of n-butanal can cause systemic toxicity (indicated by the results of the acute dermal toxicity studies) however the data are insufficient to derive a quantitative dose descriptor for systemic effects following dermal exposure. The substance is a skin irritant (although is not classified as such), therefore local effects will dominate and exposure should be minimised by the use of appropriate PPE.

 

Systemic effects (inhalation)

 

The available studies do not show any systemic toxicity following repeated inhalation exposure; findings in these studies are dominated by local effects. A systemic DNEL for inhalation exposure is not derived as the local DNEL for inhalation effects will be protective of any systemic toxicity.

 

Local effects (dermal)

 

The substance is a skin irritant (although is not classified as such); adequate dose-response data are not available for this effect and a quantitative dose descriptor (and hence a DNEL) is not derived. Exposure should be minimised by the use of appropriate PPE.

 

Local effects (inhalation)

 

The repeated inhalation toxicity studies report an overall NOAEC of 150 mg/m3 for local irritant effects. According to REACH guidance (Chapter R8), the use of assessment factors is considered:

 

Assessment factor of 1 for interspecies variation (default for local effects)

Assessment factor of 5 for intraspecies variation (default for workers)

Assessment factor of 1 for exposure duration (for short-term effects); assessment factor of 2 for exposure duration (for long-term effects)

Assessment factor of 1 for dose-response (default)

Assessment factor of 1 for database quality (default)

 

Combination of the assessment factors therefore gives overall factors of 5 for short-term exposure and 10 for long-term exposure. Based on the relevant NOAEC of 150 mg/m3. DNEL values of 30 mg/m3 (for short-term exposure) and 15 mg/m3 (for long-term exposure) are derived.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

The substance is used solely as an intermediate, therefore exposure of the general population is not predicted and DNEL derivation is not required.