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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
93 mg/m³
DNEL related information
Overall assessment factor (AF):
3
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The worker long-term systemic DNELs are based on both the Indicative Occupational Exposure Limit (IOEL) for n-hexane and test data results for commercial hexane. This analysis assumes that the maximum n-hexane content could be as much as 80%.

The worker inhalation DNEL for n-hexane is 75 mg/m3 based on the IOEL for n-hexane, and assuming that the worker inhalation DNEL for hexane solvent with < 5% n-hexane is 5306 mg/m3 based on animal test data (see documentation that follows), the DNEL for hexane solvent containing between 5 and 80% n-hexane is calculated as follows:

worker inhalation DNEL = (0.8/75) + (0.2/5306) = 93 mg/m3.

The long-term systemic DNELs for this substance were derived based on animal data and were calculated as follows:

Inhalation:

Dose descriptor: NOAEC: 31680 mg/m3(9000 ppm), inhalation route of exposure

Basis for dose descriptor:  Commercial hexane is a mixture of six-carbon isomers comprised primarily of n-hexane, 3-methylpentane, methylcyclopentane, and 2-methylpentane. API (1990) exposed rats via inhalation to commercial hexane (53.45% n-hexane) for 6 h/day, 5 days/week, for 13 weeks and no neurological effects were found. Daughtrey et al. (1999) exposed rats and mice to commercial hexane (~52% n-hexane) via inhalation for 6 h/day, 5 days/week for 2 years. A complete histopathological examination was conducted and no human relevant effects were detected.

Rationale for selection of dose descriptor:  Rats were exposed to commercial hexane (53.45% n-hexane) for 6 h/day, 5 days/week, for 13 weeks (API, 1990), and rats and mice were exposed to commercial hexane (~52% n-hexane) for 6 h/day, 5 days/week for 2 years (Daughtrey et al., 1999).

Rationale for selection of dose descriptor:  There were no adverse effects observed at the highest concentration tested in the rats exposed to 31680 mg/m3commercial hexane in both studies. In the Daughtrey et al. (1999) study, there was an increased incidence of hepatocellular (combined adenomas and carcinomas) neoplasms in female mice but tumors were not observed in rats of either sex or in male mice. The neoplasms which were increased were deemed of questionable relevance to human health risk assessment. Based on the data from both of these key studies, the NOAEC was established as 31680 mg/m3commercial hexane.

 

Dose descriptor: NOAEC, highest concentration tested

Modification of starting value: 6 hours/day, 5 days/week, for 2 years. Adjustment needed for an 8 hour day

             31680 mg/m3 * (6 h/8 h) * (6.7 m3 / 10 m3) = 15919 mg/m3

Using an assessment factor of 3, the worker inhalation DNEL based on commercial hexane data is 5306 mg/m3.

Dermal Route:

Dose descriptor: NOAEC: 31680 mg/m3(9000ppm), inhalation route of exposure, same as described above.

Modification of starting value: 6 hours/day, 5 days/week, for 2 years. Adjustment needed for an 8 hour day

             31680 mg/m3* (6h/8h) = 23760 mg/m3

Modification of starting value: Route to route extrapolation. ECHA. May 2008. “Guidance on Information Requirements and Chemical Safety Assessment Chapter R.8: Characterisation of Dose [Concentration]- Response for Human Health. Figure R. 8-3. page 27. 

Corrected inhalatory NOAEC = Oral NOAEL * (1/sRVrat)*(ABSoral rat/ABSinh human)*(sRVhuman/wRV)

23760 mg/m3= (1/0.38 m3/kg/d) * (1/1) * (6.7 m3/10m3) = 41893 mg/kg

 

Corrected dermal NOAEL = Oral NOAEL * (ABSoral-rat/ABSdermal-rat)*(ABSdermal-rat/ABSdermal-human

41892 mg/kg * (1/1) * (1/1) = 41893 mg/kg

 

Applying an assessment factor of 3, the calculated long-term dermal DNEL based on commercial hexane data is 13964 mg/kg/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The general population long-term systemic DNELs were derived from the DNELs calculated for workers. The worker DNELs are based on both the IOEL for n-hexane and test data results for commercial hexane. The analysis assumed that the maximum n-hexane content could be as much as 80%. Please see the discussion of the calculation of the worker DNELs.

The worker inhalation DNEL for hexane solvent containing between 5 and 80% n-hexane is 93 mg/m3. To derive the general population inhalation DNEL, this number was multiplied by 10/20 to correct for difference between worker and general population ventilation rates, 5/7 to correct for days of the week to which the general population could be exposed, and 3/5 to utilise the assessment factor of 5 for the intraspecies differences. The result of this calculation is 20 mg/m3.

The general population dermal and oral DNELs for this substance were calculated based on the general population inhalation DNEL:

20 mg/kg/day * 20 / 60 = 7 mg/kg/day (but proposing 6 mg/kg/day for oral for consistency with other analyses)