Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Worker DNELs for Low boiling point naphthas (gasolines)

 

Effect

Route

DNEL

Dose Descriptor

Modified Dose Descriptor and Assessment Factors

Acute Exposure

Systemic

Dermal

(b)

 

 

Inhalation

1300 mg/m3/15 min

4320 mg/m3/1 h

(LOAEC based on for neuromuscular symptoms in human volunteers)

Dose descriptor was modified to correct starting point of 3859 mg/m3/15 min by adjustment for duration of exposure, LOAEC to NOAEC, and ventilation rate of workers. Then AF of 3 was applied for intraspecies differences.

Local

Dermal

 (c)

 

 

Inhalation

1100 mg/m3/15 min

2400 mg/m3/1 h

(LOAEC based on irritation of nose and throat in human volunteers)

Dose descriptor was modified to correct starting point of 3200 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 3 was applied for intraspecies differences.

Long-Term Exposure

Systemic (a)

Dermal

(b)

 

 

Inhalation

(b)

 

 

Local

Dermal

(c)

 

 

Inhalation

840 mg/m3/8h 

10,000 mg/m3/6 h

(NOAEC based on red nasal discharge in rats exposed by inhalation for 6 h/day, 5 days/wk for 13 wk)

Dose descriptor was modified to correct starting point of 5025 mg/m3/8-h day by adjustment for duration of daily exposures and ventilation rate of workers. Then AF of 6 was applied for inter- and intraspecies differences and for overall duration of exposure.

a) Long-term systemic effects include non-reproductive effects and developmental/reproductive effects. Lowest DNEL is shown.

b) No hazard identified for this route (data available)

c) The data do not allow setting a DNEL.

Worker DNELs for Low boiling point naphthas (gasolines) (R45/46; R62/63)

 

Effect

Route

DNEL

Dose Descriptor

Modified Dose Descriptor and Assessment Factors

Acute Exposure

Systemic

Dermal

(c) (a)

 

 

Inhalation

1300 mg/m3/15 min (a)

4320 mg/m3/h

(LOAEC based on for neuromuscular symptoms in human volunteers)

Dose descriptor was modified to correct starting point of 3859 mg/m3/15 min by adjustment for duration of exposure, LOAEC to NOAEC, and ventilation rate of workers. Then AF of 3 was applied for intraspecies differences.

Local

Dermal

(d)

 

 

Inhalation

1100 mg/m3/15 min

2400 mg/m3/h

(LOAEC based on irritation of nose and throat in human volunteers)

Dose descriptor was modified to correct starting point of 3200 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 3 was applied for intraspecies differences.

Long-Term Exposure

Systemic (b)

Dermal

(c) (a)

 

 

Inhalation

(c) (a)

 

 

Local

Dermal

(d)

 

 

Inhalation

840 mg/m3/8h

10,000 mg/m3/6 h

(NOAEC based on red nasal discharge in rats exposed by inhalation for 6 h/day, 5 days/wk for 13 wk)

Dose descriptor was modified to correct starting point of 5025 mg/m3/8-h day by adjustment for duration of daily exposures and ventilation rate of workers. Then AF of 6 was applied for inter- and intraspecies differences and for overall duration of exposure.

a) Additional consideration should be given to an inhalation DMEL-worker for benzene of 1 ppm if benzene air concentrations are sufficiently high. A dermal reference value for workers of 23.4 mg of benzene/kg/day [1% absorption of benzene from benzene-containing petroleum naphtha streams via the skin] should be considered if dermal exposure is expected.

b) Long-term systemic effects include non-reproductive effects and developmental/reproductive effects. Lowest DNEL is shown.

c) No hazard identified for this route (data available)

d) The data do not allow setting a DNEL.

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

General Population - Hazard for the eyes

Additional information - General Population

General Population DNELs for Low boiling point naphthas (gasolines)

 

Effect

Route

DNEL

Dose Descriptor

Modified Dose Descriptor and Assessment Factors

Acute Exposure

Systemic

 

Dermal

(a)

 

 

Inhalation

1200 mg/m3/15 min

4320 mg/m3/h

(LOAEC based on for neuromuscular symptoms in human volunteers)

Dose descriptor was modified to correct starting point of 5760 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 5 was applied for intraspecies differences.

Local

Dermal

(e)

 

 

Inhalation

640 mg/m3/15 min

2400 mg/m3/h

(LOAEC based on irritation of nose and throat in human volunteers)

Dose descriptor was modified to correct starting point of 3200 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 5 was applied for intraspecies differences.

Long-Term Exposure

Systemic (b)

Dermal

(a)

 

 

Inhalation

(a)

 

 

Oral

(d)

 

 

Local

Dermal

(e)

 

 

Inhalation

180 mg/m3/24h

10,000 mg/m3/6 h

(NOAEC based on red nasal discharge in rats exposed by inhalation for 6 h/day, 5 days/wk for 13 wk)

Dose descriptor was modified to correct starting point of 1785 mg/m3/24-h day by adjustment for duration of daily exposures and number of exposures per week. Then AF of 10 was applied for inter- and intraspecies differences and for overall duration of exposure.

a) No hazard identified for this route (data available)

b) Long-term systemic effects include developmental/reproductive effects. Lowest DNEL is shown.

c) A DNEL for short-term oral exposures of the general population was not calculated for the reasons given below.

a) Acute oral toxicity studies with gasoline or naphtha streams did not result in significant adverse effects with doses at or above the limit dose.

b) Oral contact with gasoline and naphtha streams should be avoided because of the aspiration hazard. Gasoline and naphtha streams are labelled R65 (Harmful, may cause lung damage if swallowed).

d) A DNEL for long-term oral exposures of the general population was not calculated for the reasons given below. The hazard from long-term oral exposures of the general population may be more dependent on the presence of benzene or toluene in gasoline; appropriate measures should be taken based on the levels of those substances.

a) Dermal or inhalation repeat-dose studies with gasoline or naphtha streams did not result in adverse systemic effects with doses at or above the limit dose.

b) Aside from potential neuromuscular effects from very high doses, acute exposures to gasoline and naphtha streams also have not resulted in significant adverse systemic effects.

c) Data on oral exposures were not available (possibly because it was not considered to be a relevant route).

e) The data do not allow setting a DNEL.

General Population DNELs for Low boiling point naphthas (gasolines) (R45/46; R62/63)

 

Effect

Route

DNEL

Dose Descriptor

Modified Dose Descriptor and Assessment Factors

Acute Exposure

Systemic

 

Dermal

 (a)(c)

 

 

Inhalation

1200 mg/m3/15 min (a)

4320 mg/m3/h

(LOAEC based on for neuromuscular symptoms in human volunteers)

Dose descriptor was modified to correct starting point of 5760 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 5 was applied for intraspecies differences.

Local

Dermal

(e)

 

 

Inhalation

640 mg/m3/15 min

2400 mg/m3/h

(LOAEC based on irritation of nose and throat in human volunteers)

Dose descriptor was modified to correct starting point of 3200 mg/m3/15 min by adjustment for duration of exposure and LOAEC to NOAEC. Then AF of 5 was applied for intraspecies differences.

Long-Term Exposure

Systemic (b)

Dermal

 (a)(c)

 

 

Inhalation

(a) (c)

 

 

Oral

 (a) (d)

 

 

Local

Dermal

(e)

 

 

Inhalation

180 mg/m3/24h

10,000 mg/m3/6 h

(NOAEC based on red nasal discharge in rats exposed by inhalation for 6 h/day, 5 days/wk for 13 wk)

Dose descriptor was modified to correct starting point of 1785 mg/m3/24-h day by adjustment for duration of daily exposures and number of exposures per week. Then AF of 10 was applied for inter- and intraspecies differences and for overall duration of exposure.

a) Additional consideration should be given to an inhalation DMEL-general population for benzene of 1 ppb if benzene air concentrations are sufficiently high. Using this air concentration reference value for benzene in air of 1 ppb (3.5 microgram/m3) and assuming a default inhalation rate of 20 m3/day and a body weight of 70 kg yields a reference value for indirect exposure of 1.0 microgram benzene/kg/d. The ratio of benzene to total gasoline vapor utilized was 0.01. Thus, the resulting reference value utilized for indirect exposure of man via the environment is 100 micrograms total naphtha hydrocarbon containing benzene /kg/d (see CSR Section 10). A dermal reference value for general population of 23.4 micrograms of benzene/kg/day [1% absorption of benzene from benzene-containing petroleum naphtha streams via the skin], should be considered if dermal exposure is expected. An oral reference value for general population, of 0.234 micrograms of benzene/kg/day, from benzene-containing petroleum naphtha streams in the environment should be considered if exposure via the oral route is expected (this is not expected).

b) Long-term systemic effects include developmental/reproductive effects. Lowest DNEL is shown.

c) No hazard identified for this route (data available)

d) A DNEL for long-term oral exposures of the general population was not calculated for the reasons given below. The hazard from long-term oral exposures of the general population may be more dependent on the presence of benzene or toluene in gasoline; appropriate measures should be taken based on the levels of those substances.

c) Dermal or inhalation repeat-dose studies with gasoline or naphtha streams did not result in adverse systemic effects with doses at or above the limit dose.

d) Aside from potential neuromuscular effects from very high doses, acute exposures to gasoline and naphtha streams also have not resulted in significant adverse systemic effects.

d) Data on oral exposures were not available (possibly because it was not considered to be a relevant route).

e) The data do not allow setting a DNEL.