[OrganicDan96]

I was recently filling out some health and safety for an upcoming reaction and I noticed according to the Sigma Aldrich SDS that it has the hazard code H304 May be fatal if swallowed and enters airways among others, however the same sds suggests it has an LD50 (rat) of 16g/kg which seems very high, which seems to be a bit of a contradiction to me.

for comparison ethanol has an LD50 (rat) of 10.4g/kg

so my question is why is hexane so toxic?

[Babcock_Hall]

This is a bit of a shot in the dark, but I have a vague recollection that hexane is a substrate for cytochrome P-450 and that this might be more toxic than hexane itself.
EDT
See for example: https://www.ncbi.nlm.nih.gov/pubmed/2009082
"The results suggest that MiBK [methyl isobutyl-ketone] selectively induces cytochrome P450 isozymes leading to the metabolic activation of the weak neurotoxicant n-hexane to the potent neurotoxicant 2,5-hexanedione (2,5-HD)."

[pgk]

LD50 value depends on the administration route, as well as on the animal species that is tested.
In the hexane MDS section 11, it is clearly mentioned that LD50 = 16 g/kg refers to the oral administration in rats.
It also mentioned therein that the lethal concentration in air for the 50% of the tested rats, is LC50 = 172 mg/Lx4h and which is too low.
On the other hand, hexane is a volatile compounds and risks to simultaneously enter in the respiratory tract when swallowed and thus, it may be fatal that way due to (among other) possible pulmonary edema.
PS: All highly volatile compounds must be considered as potentially fatal if swallowed, regardless their relatively high LD50 value (gasoline included).

[DrCMS]

As others have pointed out all volatile solvents are an aspiration hazard.  However, chronic exposure to hexane can cause peripheral neuropathy.  That is not reflected in the LD50 which is a measure of acute toxicity.

[OrganicDan96]

As others have pointed out all volatile solvents are an aspiration hazard.  However, chronic exposure to hexane can cause peripheral neuropathy.  That is not reflected in the LD50 which is a measure of acute toxicity.

interesting but that would not explain the fatel if swallowed and inhaled which would be explained by accute toxicity. the chemical does have causes damage to organs hazard as well which would cover this

[DrCMS]

H304 has NOTHING to do with acute toxicity of the material and EVERYTHING to do with its volatility/vapour pressure.

[OrganicDan96]

i understand that, however why do other high vapour pressure solvents such as diethyl ever not have H304? one suggestion i had from someone recently was that hexane is the right size for some biological targets which i guess relates to what Babcock_Hall said.

[OrganicDan96]

this is interesting
https://formpaksupport.desk.com/customer/en/portal/articles/2108466-hydrocarbons-aspiration-hazard-h304
https://www.schc.org/assets/docs/ghs_info_sheets/aspiration_hazard.pdf
these suggests there is some factor with viscosityand that some chemicals can be given H304 just based on their viscosity and is true for hydrocarbons. this may explain why other solvents don't get H304

[Babcock_Hall]

I am not going to be of much help with respect to H304 or related issues.  However for those unfamiliar with it, the cytochrome P-450 family of enzymes adds oxygen to various atoms, sometimes in the form of a hydroxyl group.  There are some references to sampling and work-up of urine samples here:  https://oem.bmj.com/content/oemed/48/8/568.full.pdf

See also:  https://books.google.com/books?id=_0dk3--pmsYC&pg=PA82&lpg=PA82&dq=hexane+conversion+to+hexane+2,5-dione&source=bl&ots=yCxU8IAo6B&sig=ACfU3U0zAHP6a-M954_bSKjOeDk6hrWR1A&hl=en&sa=X&ved=2ahUKEwip8qO6sM7jAhUDLKwKHRkvCZ84ChDoATAIegQIBxAB#v=onepage&q=hexane%20conversion%20to%20hexane%202%2C5-dione&f=false

[pgk]

Diethyl ether is not subjected to H3O4 labeling due to the relatively high limit of lethal concentration in air (high LC50 value):
LC50 Inhalation-Mouse: 31000 ppmx30 min, Remarks: Behavioral: Convulsions or effect on seizure threshold.
LC50 Inhalation-Rat: 32000 ppmx4h
(LC values are taken from a diethyl ether MSDS.)
 

[OrganicDan96]

I see i guess that makes sense, thank you

[hollytara]

Years ago a colleague who had extensively worked with hexane told me he had hexane induced neuropathy - numbness in his fingertips from the hexane exposure.