Benzene, C15-16-alkyl derivs.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

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:

DNEL (Derived No Effect Level)

Value:

7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

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:

9.6 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Additional information - workers

For the human health endpoints, the most relevant/critical DNELs for Benzene, C15 -16 -alkyl derivs. are considered to be the DNELlong-term for worker dermal and inhalation exposures and for consumer oral, dermal and inhalation exposures. The worker dermal and inhalation DNELlong-term were calculated to be 9.6 mg/kg bw/day and 7.0 mg/m3, respectively. The consumer DNELlong-term for oral, dermal and inhalation exposures were calculated to be 0.5 mg/kg bw/day, 4.8 mg/kg bw/day and 1.8 mg/m3, respectively.

Discussion

Benzene, C15 -16 -alkyl derivs. is not considered to be hazardous to human health. Acute toxicity studies for read-across source substances via the oral and dermal exposure routes resulted in no mortality or other signs of toxicity at the limit doses. No significant effects were observed in acute skin and eye irritation studies, with only minimal effects observed at 100% dermal doses. In repeated dose studies the only effects were reduced body weight gain. Effects on survival and weight gain in the F1 and F2 generations in a reproductive toxicity study were observed at doses of 500 mg/kg bw/d and above. Effects in a developmental study were only observed at doses that were maternally toxic.

In addition, mutagenicity studies using both in vitro and in vivo methods demonstrate that the test substance was not mutagenic.

Because of the lack of significant toxicity observed in the suite of toxicity tests, the DNEL derivation was focused on the worst case situations, that is, long-term exposure to workers via both the oral and dermal routes. The NOAEL used to derive the DNELs was the lowest NOAEL from the reproductive toxicity chronic test with rats. The calculated DNELlong-term values for dermal and inhalation exposures were 9.6 mg/kg bw/day and 7.0 mg/m3, respectively. The calculated DNELlong-term values for consumer oral, dermal and inhalation exposures were 0.5 mg/kg bw/day, 4.8 mg/kg bw/day and 1.8 mg/m3, respectively

Benzene, C15 -16 -alkyl derivs. is not classified for any of the human health endpoints, nor is it classified as a PBT or vPvB. Benzene, C15 -16 -alkyl derivs. is classified for aspiration hazard due to its low viscosity and therefore exposure and risk characterizations have been completed.

DNEL long-term, workers, inhalation

For this DNEL, a similar procedure is applied as for the derivation of the dermal DNEL. However, since only oral long-term toxicity data are available, the oral NOAEL must first be converted to an inhalation value to use as the starting point. Using the formulae in Figure R.8-3 of Chapter R.8 (p.27) and the oral NOAEL of 50 mg/kg, the resulting inhalation NOAEC would be 88 mg/m3. Because this conversion includes interspecies exposure duration differences, no allometric scaling assessment factor is required . The remaining assessment factors are included as shown in the table below. The resulting DNELlong-term, workers, inhalation is equivalent to 7.0 mg/m3.

DNEL long-term, workers, dermal

For long-term, worker, dermal exposures, the DNEL is derived using the oral NOAEL as the starting point. This starting point oral NOAEL value must be corrected for route-to-route extrapolation. In accordance with REACH guidance document R.8, in the absence of data, no default factor (i.e. factor of 1) should be introduced for oral-to-dermal extrapolation, based on the assumption that dermal absorption will in general not be higher than oral absorption. However, for highly lipophilic substances (log Kow > 4), according to Section R.7.12.2.1 of REACH guidance document R7.C, a 10% default dermal absorption value is recommended for the purpose of risk assessment. Therefore a factor of 9.6 (ABSoral/ABSdermal = 96/10) can be used to correct the starting dose for absorption difference between routes. The next steps consist in applying assessment factors for interpecies difference, intraspecies variation, exposure duration, dose-response and quality of the database. The overall AF in this case again corresponds to 50 (see the table below). The resulting DNELlong-term, workers, dermal is equivalent to 9.6 mg /kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.8 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

25

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:

DNEL (Derived No Effect Level)

Value:

1.8 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

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:

4.8 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

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:

0.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Additional information - General Population

For the human health endpoints, the most relevant/critical DNELs for Benzene, C15 -16 -alkyl derivs. are considered to be the DNELlong-term for worker dermal and inhalation exposures and for consumer oral, dermal and inhalation exposures. The worker dermal and inhalation DNELlong-term were calculated to be 9.6 mg/kg bw/day and 7.0 mg/m3, respectively. The consumer DNELlong-term for oral, dermal and inhalation exposures were calculated to be 0.5 mg/kg bw/day, 4.8 mg/kg bw/day and 1.8 mg/m3, respectively.

Discussion

Benzene, C15 -16 -alkyl derivs. is not considered to be hazardous to human health. Acute toxicity studies via the oral and dermal exposure routes resulted in no mortality or other signs of toxicity at the limit doses. No significant effects were observed in acute skin and eye irritation studies, with only minimal effects observed at 100% dermal doses. In repeated dose studies the only effects were reduced body weight gain. Effects on survival and weight gain in the F1 and F2 generations in a reproductive toxicity study were observed at doses of 500 mg/kg bw/d and above. Effects in a developmental study were only observed at doses that were maternally toxic.

In addition, mutagenicity studies using both in vitro and in vivo methods demonstrate that the test substance was not mutagenic.

Because of the lack of significant toxicity observed in the suite of toxicity tests, the DNEL derivation was focused on the worst case situations, that is, long-term exposure to workers via both the oral and dermal routes. The NOAEL used to derive the DNELs was the lowest NOAEL from the reproductive toxicity chronic test with rats. The calculated DNELlong-term values for dermal and inhalation exposures were 9.6 mg/kg bw/day and 7.0 mg/m3, respectively. The calculated DNELlong-term values for consumer oral, dermal and inhalation exposures were 0.5 mg/kg bw/day, 4.8 mg/kg bw/day and 1.8 mg/m3, respectively

Benzene, C15 -16 -alkyl derivs. is not classified for any of the human health endpoints, nor is it classified as a PBT or vPvB. Benzene, C15 -16 -alkyl derivs. is classified for aspiration hazard due to its low viscosity and therefore exposure and risk characterizations have been completed.

DNEL long-term, consumers, inhalation

For this DNEL, a similar procedure is applied as for the derivation of the other DNELs. However, since no long-term inhalation toxicity data are available, the oral NOAEL must first be converted to an inhalation value to use as the starting point. Using the formula for the general population in Figure R.8-3 of Chapter R.8 (p.27) and the oral NOAEL of 50 mg/kg, the resulting inhalation NOAEC would be 44 mg/m3. Because this conversion includes interspecies exposure duration differences, no allometric scaling assessment factor is required. The remaining assessment factors are included as shown in the table below. The resulting DNELlong-term, consumers, inhalation is equivalent to 1.8 mg/m3.

DNEL long-term, consumers, dermal

For long-term, consumer, dermal exposures, the DNEL is derived using the oral NOAEL as the starting point. This starting point oral NOAEL value must be corrected for route-to-route extrapolation. In accordance with REACH guidance document R.8, in the absence of data, no default factor (i.e. factor of 1) should be introduced for oral-to-dermal extrapolation, based on the assumption that dermal absorption will in general not be higher than oral absorption. However, for highly lipophilic substances (log Kow > 4), according to Section R.7.12.2.1 of REACH guidance document R7.C, a 10% default dermal absorption value is recommended for the purpose of risk assessment. Therefore a factor of 9.6 (ABSoral/ABSdermal = 96/10) can be used to correct the starting dose for absorption difference between routes. The next steps consist in applying assessment factors for interpecies difference, intraspecies variation, exposure duration, dose-response and quality of the database. The overall AF in this case again corresponds to 100 (see the table below). The resulting DNELlong-term, consumers, dermal is equivalent to 4.8 mg /kg bw/day.

DNEL long-term, consumers, oral

The starting point oral value is taken from the reproductive toxicity study and is based on reduced survival and reductions in body weight in the F1 and F2 generations. No corrections for route-to-route extrapolation are necessary. Next, assessment factors (AF) are applied for interspecies differences, intraspecies variation, exposure duration, dose-response and quality of the database, as described in Section R.8.4.3 of REACH guidance document R.8. For consumers, the general population AF of 10 is used for intraspecies variation. Because of this, the overall AF in this case corresponds to 100 (see the table below). The resulting DNELlong-term, consumers, oral is equivalent to 0.5 mg /kg bw/day.