Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 035 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
773 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
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

Workers - Hazard for the eyes

Additional information - workers

The pattern of identified uses described for hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane includes short-term peak exposure by inhalation and the dermal route as well as long-term repeated exposure by inhalation and the dermal route. In the case of short-term exposure, it is not possible to derive a DNEL for systemic effects, since CNS toxicity (narcotic effects) and local irritation on the skin are the leading effects.Therefore, appropriate risk management measures will be identified.

Assessment factors were chosen on the basis of ECETOC (2003) and other, more recent, information. For route to route extrapolation, absorption differences were not taken into account.

 

CNS Effects

In studies in rodents, 8 hours of exposure to n-octane (Lammers et al., 2010) did not produce any acute CNS effects at levels up to 14,000 mg/m3. Similarly, there were no acute CNS effects associated with exposure to iso-octane for 8 hours at 14,000 mg/m3 (Lammers et al., 2001a). In a study of a mixed C7 cycloparaffinic solvent, there was evidence of acute CNS effects at 14,000 mg/m3, but no effects at 4200 mg/m3 (Lammers et al., 2001a). In older studies, the anaesthetic levels for n-heptane and iso-octane in mice were reported as greater than 8000 ppm (approximately 32,000 mg/m3 ) (Swan et al., 1974).

 

In humans heptane was reported to produce a slight vertigo in 6 minutes at a concentration of 1000 ppm (approximately 4000 mg/m3) (Patty and Yant, 1929).

 

In summary the animal and human data indicate that the worker long term inhalation DNEL (approximately 2000 mg/m3) is also protective for short term effects including acute CNS effects and respiratory irritation.

 

References:

 

Lammers , J. et al. (2010). Neurobehavioral effects of acute exposures to(n-) paraffins. International Journal of Toxicology (submitted for publication).

 

Lammers, J. et al. (2001a). The effects of short term inhalatory exposure to iso-octane on behavior in the rat. TNO Report V99.430. (unpublished laboratory report).

 

Lammers, J. et al. (2001b). The effects of short-term inhalatory exposure to Cypar 7 on behavior in the rats. TNO Report V99.1115. (unpublished laboratory report).

 

Swan, H. et al. (1974). Acute inhalation toxicology of volatile hydrocarbons. American Industrial Hygiene Association Journal 35:511-518.

 

Patty, F., and Yant, W. (1929). Odor intensity and symptoms produced by commercial propane, butane, pentane, hexane and heptane. Bureau of Mines. R.I. 2979.

 

ECETOC (2003). Derivation of assessment factors for human health risk assessment. Technical report No. 86, (European Centre for Ecotoxicology and Toxicology of Chemicals).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
608 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
699 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
699 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The pattern of identified uses described for hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, <5% n-hexane includes short-term peak exposure by inhalation and the dermal route as well as long-term repeated exposure by inhalation and the dermal route. In the case of short-term exposure, it is not possible to derive a DNEL for systemic effects, since CNS toxicity (narcotic effects) and local irritation on the skin are the leading effects.Therefore, appropriate risk management measures will be identified.

Assessment factors were chosen on the basis of ECETOC (2003) and other, more recent, information. For route to route extrapolation, absorption differences were not taken into account.

 

CNS Effects

In studies in rodents, 8 hours of exposure to n-octane (Lammers et al., 2010) did not produce any acute CNS effects at levels up to 14,000 mg/m3. Similarly, there were no acute CNS effects associated with exposure to iso-octane for 8 hours at 14,000 mg/m3 (Lammers et al., 2001a). In a study of a mixed C7 cycloparaffinic solvent, there was evidence of acute CNS effects at 14,000 mg/m3, but no effects at 4200 mg/m3 (Lammers et al., 2001a). In older studies, the anaesthetic levels for n-heptane and iso-octane in mice were reported as greater than 8000 ppm (approximately 32,000 mg/m3 ) (Swan et al., 1974).

 

In humans heptane was reported to produce a slight vertigo in 6 minutes at a concentration of 1000 ppm (approximately 4000 mg/m3) (Patty and Yant, 1929).

 

In summary the animal and human data indicate that the worker long term inhalation DNEL (approximately 2000 mg/m3) is also protective for short term effects including acute CNS effects and respiratory irritation.

 

References:

 

Lammers , J. et al.(2010). Neurobehavioral effects of acute exposures to(n-) paraffins. International Journal of Toxicology (submitted for publication).

 

Lammers, J. et al. (2001a). The effects of short term inhalatory exposure to iso-octane on behavior in the rat. TNO Report V99.430. (unpublished laboratory report).

 

Lammers, J. et al. (2001b). The effects of short-term inhalatory exposure to Cypar 7 on behavior in the rats. TNO Report V99.1115. (unpublished laboratory report).

 

Swan, H. et al. (1974). Acute inhalation toxicology of volatile hydrocarbons. American Industrial Hygiene Association Journal 35:511-518.

 

Patty, F., and Yant, W. (1929). Odor intensity and symptoms produced by commercial propane, butane, pentane, hexane and heptane. Bureau of Mines. R.I. 2979.

 

ECETOC (2003). Derivation of assessment factors for human health risk assessment. Technical report No. 86, (European Centre for Ecotoxicology and Toxicology of Chemicals).