Hydrocarbons, C5-C7, n-alkanes, isoalkanes, < 5% n-hexane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 474 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

neurotoxicity

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

210 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

Explanation for the modification of the dose descriptor starting point:

Please refer to discussion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

There are no data available on hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane. However, there are reliable data available considered suitable for read-across using the analogue approach.The target substance is a hydrocarbon solvent with carbon numbers in the range of C5 to C6. The main constituents of the mixed solvent consist of about 43% of C6 species and about 57% of C5 species. n-Hexane is only present in concentrations < 5% of the total volume.The source substances chosen for read-across have similar toxicological properties as the target substance. There is only one distinguishing characteristic for n-hexane. n-Hexane has unique toxicological properties due to its ability to be metabolized to the neurotoxic metabolite 2,5-hexanedione. Other C6 species will not be metabolized to 2,5-hexanedione. For this reason, n-hexane and hydrocarbon solvents containing n-hexane at levels greater than 5% represent a worst case scenario.Taking into account all available data, animal and human toxicity data as well as environmental fate and effects data show that source substances have similar (eco-)toxicological and environmental fate properties as the target substance.Therefore, read-across is performed based on an analogue approach (for details please refer to the analogue justification which is attached in section 13 of the technical dossier).

 

No DNELs have been derived for the short-term dermal and inhalation exposure of the test substance for workers, since CNS toxicity (narcotic effects) and local irritation on the skin are the leading effects. Therefore, appropriate risk management measures will be identified.

No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of the test substance.

 

In order to take into account the composition of the UVCB test substance, especially the n-hexane content, the reciprocal calculation procedure (RCP) was used to derive the DNELs. This procedure follows the American Conference of Governmental Industrial Hygienists' (ACGIH) advice for "complex mixtures" like UVCB substances and is recommended by the U. K. Health and Safety Executive for occupational exposure limit (OEL) calculations by hydrocarbon solvent manufacturers. The RCP is justified, as the toxicological properties of the components are additive and the differences between the vapour and liquid compositions do not substantially affect the calculated exposure limits.

In a first step,the main constituents of the test substance were identified by the registrant: 43% C6 species and 57% C5 species. As starting points for the derivation of DNELs by the RCP the lowest available long-term inhalation DNEL derived for workers for C6 species (880 mg/m³) and the indicative OEL for n-pentane (3000 mg/m³) were used.

 

The starting point for the derivation of the inhalation DNEL is a NOAEC of 10504 mg/m³ from a subchronic inhalation toxicity study of commercial hexane (40-55% n-hexane, >10% methylcyclopentane) in rats (API, 1990).

In order to account for differences between experimental and human exposure conditions, the starting point was modified according to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012”.

The following corrections were made:

Correction for exposure duration: 6 h/8 h

Correction for respiratory volume (for workers, in case of 8 h exposure / respiratory light activity for worker): 6.7 m³/10 m³

Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:

Corrected NOAEC = 10504 mg/m³ * (6 h / 8h) * (6.7m³/ 10m³) = 5278 mg/m³

 

The following assessment factors based on ECETOC TECHNICAL REPORT No. 110 (October, 2010) were applied to the corrected NOAEC:

Extrapolation of exposure duration (sub-chronic to chronic): 2

Intraspecies differences (worker): 3

The inhalation DNEL for commercial hexane is therefore:

DNEL = 5278 mg/m³ / [(2 (subchronic to chronic) x 3 (intraspecies)] = 880 mg/m³

 

Derivation of DNELs by thereciprocal calculation procedure:

The DNELs for hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane containing 43% C6 species and 57% C5 species are calculated as follows:

The body weight used in the calculation is 70 kg for the workers.

DNEL long-term inhalation: 0.43/880 + 0.57/3000 = 1/DNEL --> DNEL = 1474 mg/m³

DNEL long-term dermal = 1474 mg/m³ x 10 m³/day / 70 kg = 210 mg/kg bw/day

Absorption differences were not taken into account.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

315 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

neurotoxicity

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

105 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

Explanation for the modification of the dose descriptor starting point:

Please refer to discussion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

105 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

Explanation for the modification of the dose descriptor starting point:

Please refer to discussion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

There are no data available on hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane. However, there are reliable data available considered suitable for read-across using the analogue approach.The target substance is a hydrocarbon solvent with carbon numbers in the range of C5 to C6. The main constituents of the mixed solvent consist of about 43% of C6 species and about 57% of C5 species. n-Hexane is only present in concentrations < 5% of the total volume.The source substances chosen for read-across have similar toxicological properties as the target substance. There is only one distinguishing characteristic for n-hexane. n-Hexane has unique toxicological properties due to its ability to be metabolized to the neurotoxic metabolite 2,5-hexanedione. Other C6 species will not be metabolized to 2,5-hexanedione. For this reason, n-hexane and hydrocarbon solvents containing n-hexane at levels greater than 5% represent a worst case scenario.Taking into account all available data, animal and human toxicity data as well as environmental fate and effects data show that source substances have similar (eco-)toxicological and environmental fate properties as the target substance.Therefore, read-across is performed based on an analogue approach (for details please refer to the analogue justification which is attached in section 13 of the technical dossier).

 

No DNELs have been derived for the short-term dermal and inhalation exposure of the test substance for the general population, since CNS toxicity (narcotic effects) and local irritation on the skin are the leading effects. Therefore, appropriate risk management measures will be identified.

No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of the test substance.

 

In order to take into account the composition of the UVCB test substance, especially the n-hexane content, the reciprocal calculation procedure (RCP) was used to derive the DNELs. This procedure follows the American Conference of Governmental Industrial Hygienists' (ACGIH) advice for "complex mixtures" like UVCB substances and is recommended by the U. K. Health and Safety Executive for occupational exposure limit (OEL) calculations by hydrocarbon solvent manufacturers. The RCP is justified, as the toxicological properties of the components are additive and the differences between the vapour and liquid compositions do not substantially affect the calculated exposure limits.

In a first step,the main constituents of the test substance were identified by the registrant: 43% C6 species and 57% C5 species. As starting points for the derivation of DNELs by the RCP the lowest available long-term inhalation DNEL derived for workers for C6 species (880 mg/m³) and the indicative OEL for n-pentane (3000 mg/m³) were used.

 

The starting point for the derivation of the inhalation DNEL is a NOAEC of 10504 mg/m³ from a subchronic inhalation toxicity study of commercial hexane (40-55% n-hexane, >10% methylcyclopentane) in rats (API, 1990).

In order to account for differences between experimental and human exposure conditions, the starting point was modified according to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012”.

The following corrections were made:

Correction for exposure duration: 6 h/24 h and 5 d/7 d

Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:

Corrected NOAEC = 10504 mg/m³ * (6 h / 8h) * (5 d/ 7 d) = 1876 mg/m³

 

The following assessment factors based on ECETOC TECHNICAL REPORT No. 110 (October, 2010) were applied to the corrected NOAEC:

Extrapolation of exposure duration (sub-chronic to chronic): 2

Intraspecies differences (general population): 5

The inhalation DNEL for commercial hexane is therefore:

DNEL = 1876 mg/m³ / [(2 (subchronic to chronic) x 5 (intraspecies)] = 188 mg/m³

 

Derivation of DNELs by the reciprocal calculation procedure:

The DNELs for hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane containing 43% C6 species and 57% C5 species are calculated as follows:

Correction for respiratory volume (Respiratory volume light activity for worker / 24 h exposure): 10 m³/ 20 m³

Correction for exposure duration: 5 d/7 d

Intraspecies differences (worker / general population): 3/5

The body weight used in the calculation is 60 kg for the general population.

DNEL long-term inhalation: 0.43/188 + 0.57/ (3000 x (10/20) x (5/7) x (3/5)) = 1/DNEL --> DNEL = 315 mg/m³

DNEL long-term dermal = 315 mg/m³ x 20 m³/day / 60 kg = 105 mg/kg bw/day

DNEL long-term oral = 105 mg/kg bw/day

In the absence of any reliable information, dermal and oral absorption is assumed to be 100% for the test substance. This assumption results in the identical DNELs for the dermal and oral exposure route.