1,6-dichlorohexane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.17 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEC

Value:

185.13 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics as outlined in the Discussion.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "Workers" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

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:

3.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

420 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A dermal absorption of 50% is assumed as a worst case scenario.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point)

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for differences between rats and humans is used.

AF for other interspecies differences:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics as outlined in the discussion.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "Workers" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole database is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factor is required. Please refer to the Discussion.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

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

General

 

DNEL derivation for the substance 1,6-dichlorohexane is performed under consideration of the recommendations of ECHA (2010). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Acute/short-term exposure - systemic effects

 

Dermal exposure: 1,6-Dichlorohexane is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation EC 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

 

Inhalation exposure: No specific DNEL for systemic acute/short-term worker exposure via inhalative route is derived. The DNEL derived for systemic long-term worker exposure via inhalative route is considered sufficiently protective.

 

Acute/short-term and long-term exposure - local effects and sensitisation

 

Skin irritation/corrosion: Based on the key skin irritation study (BASF.1963), 1,6-dichlorohexane is subject to as Category 2: irritating (H315: Causes skin irritation) according to Regulation (EC) No 1272/2008. A quantitative assessment of skin irritation is not possible since only qualitative data are available.

Eye irritation: The substance 1,6-dichlorohexane is no eye irritant based on the key study results (BASF, 1963),i.e.displays negligible potency for eye irritation. No DNEL for this local effect has to be established.

 

Respiratory irritation: There are no data available.

 

Skin sensitisation: The substance 1,6-dichlorohexane is not considered to be a skin sensitiser according to key study results (2012-0178-DGT) no DNEL for a possible skin sensitising potential is derived. Qualitatively, there is no or negligible skin sensitising potency.

 

Respiratory sensitisation: There are no data available.

 

Long-term exposure – systemic effects

 

A reproduction/developmental toxicity screening test was performed with 1,6-dichlorohexane according to OECD guideline no. 421. The NOAEL (no-observed-adverse-effect level) on the F0-generation was 210 mg/kg bw/day, p.o.. On the basis of the results obtained, the test 1,6-dichlorohexane is not considered to be subject to classification according to Regulation (EC) No 1272/2008.

 

Dermal exposure: In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the reproduction/developmental toxicity screening is identified as the relevant dose descriptor. Assuming identical values for oral and dermal absorption (worst case) and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:

 

Relevant dose descriptor (NOAEL): 210 mg/kg bw

Modification of the starting point factor: 1

Exposure duration factor (subacute to chronic): 6

Allometric scaling factor (rat-to-human): 4

Remaining interspecies differences (rat-to-human): 1

Assessment factor for intraspecies differences (worker): 5

 

There are no relevant experimental data on repeated dermal exposure. A dermal absorption of 50% is assumed as a worst case scenario.

Based on the physico-chemical properties of 1,6 -dichlorohexane (log Kow: 3.557 (25°C) and water solubility: 57 mg/L) a dermal absorption of 50% is assumed as a worst-case scenario.

In conclusion, dermal NOAEL = 2 x oral NOAEL = 420 mg/kg bw/d.

 

Worker DNEL (long-term dermal exposure)

= 420 mg/kg bw/d × 1 / (6 × 4 × 1 × 5)

= 3.5 mg/kg bw/d

 

Inhalation exposure: Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. This worker DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected) and potential local effects. The NOAEL assessed in the key repeated dose oral toxicity study is identified as the relevant dose descriptor and starting point.

 

- Modification of the starting point

Relevant dose descriptor (NOAEL): 210 mg/kg bw

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

 

Corrected inhalatory NOAEC for workers

= 210 mg/kg bw/d × (1 / 0.38 m³/kg bw/d) × 0.5 × (6.7 m³/10 m³)

= 185.13 mg/m³

 

- Calculation of the worker DNEL

Corrected inhalatory NOAEC for workers: 185.13 mg/m³

Assessment factor for intraspecies differences: 5

Exposure duration factor (subacute to chronic): 6

 

Worker DNEL (long-term inhalation exposure)

= 185.13 mg/m³ / 5 × 6

= 6.171 mg/m³, rounded to 6.17 mg/m³

 

Due to structural similarities of 1,6-dichlorohexane to n-hexane neurotoxicological effects cannot be excluded. However, since the DNEL for 1,6-dichlorohexane is well below the MAK value of n-hexane (180 mg/m³) and exposure is estimated to be low the derived inhalation DNEL (long-term, systemic) is considered to ensure an appropriate level of protection with regard to neurotoxicological effects.

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC (2010). Technical Report 110. Guidance on assessment factors to derive a DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General population is not intended to be exposed to 1,6 -dichlorohexane via inhalation or dermal route. Therefore, no DNEL (acute/short term and long-term, inhalation and dermal exposure) is derived for general population.

 

The substance is not associated with any of the following hazard categories STOT-RE 1/2, Repr. 1A/1B/2, Lact., Muta. 1A/1B/2, thus there is no identified potential to cause toxic effects if accumulated in the higher food chain. Therefore, no DNEL (long-term, oral exposure) is derived for the general population. No risk assessment for secondary poisoning is required.

 

 

References

(not included as endpoint study record)

 

- ECHA (2012) Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1 ECHA-2010 -G-19 –EN.

 

- ECHA (2011) Guidance on information requirements and chemical safety assessment. Part B: Hazard assessment. Version 2