Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 306 mg/m³
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13 964 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
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Exposure to this substance does not result in local effects, therefore, only systemic effect DNELs were calculated. The worker long-term exposure inhalation DNEL for systemic effects is 5306 mg/m3 based on animal data for commercial hexane. The worker long-term dermal DNEL for systemic effects is 5306 mg/m3 as derived from the inhalation DNEL. Note that these values are conserve in that they were derived from studies in which no effects were observed at the highest concentration tested. Note also that the value is “worst case” as the test substance contained approximately 50% n-hexane, which is the most toxic of the C6 aliphatic hydrocarbon species.

Inhalation:

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

Basis for dose descriptor:  The test substance, 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/m3 commercial 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/m3 commercial 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 systemic DNEL based on commercial hexane data is 5306 mg/m3. 

 

Dermal:

Dose descriptor: NOAEC: 31680 mg/m3 (9000ppm), inhalation route of exposure, based on same studies 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 inhalation 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:
1 131 mg/m³
Most sensitive endpoint:
neurotoxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 377 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
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 301 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

This substance is not classified as acutely toxic according to OECD GHS guidelines; therefore, acute / short-term general population DNELs were not derived.

For the general population, the long-term inhalation DNEL for systemic effects is 1131 mg/m3 (approximately 323 mg/Kg/day), the long-term dermal DNEL for systemic effects is 1377 mg/Kg/day, and the long term DNEL for oral route and systemic effects is 1301 mg/Kg/day.  Note that these values are conservative in that they were derived from studies in which no effects were observed at the highest concentration tested. Note also that the value is also “worst case” as the test substance contained approximately 50% n-hexane, which is the most toxic of the C6 aliphatic hydrocarbon species.

Inhalation:

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

Basis for dose descriptor:  The test substance, 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).

There were no adverse effects observed at the highest concentration tested in the rats exposed to 31680 mg/m3 commercial 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/m3 commercial hexane.

Dose descriptor: NOAEC, highest concentration tested

Modification of starting value: 6 hours/day, 5 days/week, for 2 years. Adjustment needed for a 24 hour day

 

31680 mg/m3 * (6h/24h) * (5 days/ 7 days) = 5657 mg/m3

Calculation of Inhalation DNEL: 5657 mg/m3/ Assessment Factor of 5 = 1131 mg/m3 (320ppm)

Dermal:

Dose descriptor: NOAEC: 31680 mg/m3 (9000 ppm), inhalation route of exposure based on the same studies as described for the inhalation DNEL above (see above for basis for dose desriptor, rationale for selection of dose descriptor, and the dose descriptor)

Modification of starting value: 6 hours/day, 5 days/week, for 2 years. Adjustment needed for a 24 hour day

 

31680 mg/m3 * (6h/24h) = 7920 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 rat)*(ABSinh rat/ABSinh-human)

 

7920mg/m3 = (1/1.15 m3/Kg/d) * (1/1) = 6887 mg/Kg

 

 

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

 

6887 mg/Kg * (1/1) * (1/1) = 6887 mg/Kg

 

Calculation of Dermal DNEL: 6887 mg/kg/day / Assessment Factor of 5 = 1377 mg/Kg/day

Oral:  

Dose descriptor: NOAEC: 31680 mg/m3 (9000 ppm), inhalation route of exposure based on the same studies as described for the inhalation DNEL above (see above for basis for dose desriptor, rationale for selection of dose descriptor, and the dose descriptor)

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 rat)*(ABSinh rat/ABSinh-human)

 

7920 mg/m3 = (1.15 m3/Kg/d) * (1/1) = 9108 mg/Kg

 

Converting from 5 days/week to daily = 9108 mg/Kg (5/7) = 6506 mg/Kg

Calculation of Oral DNEL: 6506 mg/Kg/day / Assessment Factor of 5 = 1301 mg/Kg/day