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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 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 hazard identified
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:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Only the DNEL for long-term systemic effects are derived since 1,6-hexanediol is non-irritating and acutely practically non-toxic.

 

The DNEL for long-term exposure is derived from the observed NOAEL from a 90-day repeated dose toxicity study performed according OECD guideline (BASF SE, 2014). The only effect that has been noted in high-dose males (1000 mg/kg/d) were decreases in body weights. Since no treatment-related effects of toxicological relevance have been observed at 400 mg/kg/d in neither males nor females, this dose is used as starting point for DNEL derivation

 

Worker:

 In general, the DNEL calculation is based on the observed effect level of animal studies which has to be modified.

To correct the interspecies difference between rat and human the NOAEL (400 mg/kg/d) has to be corrected by the risk assessors 0.38 mg/m3 and 6.7 m3/10 m3regarding breathing volume (rat, 8h) and frequency (worker at rest vs. at light activity), respectively. Furthermore, an additional factor of 2 has to be included considering 50% absorption following oral up-take and 100% following inhalation.

Corrected NOAEL = NOAEL / 0.38 mg/m3 x (6.7/10) / 2 = 352,6 mg/m3. Furthermore, according to ECHA guidance document R8 and ECETOC Technical Report No 110, the following assessment factors have to be taken into account:

- intraspecies differences: 5

- exposure duration: 2

- Quality of database: 1

The DNEL is calculated according to the formula DNEL = (corrected starting point)/(overall AF) as stated in R8 (ECHA, May 2008). Thus, the resulting DNEL for systemic long-term inhalative effects of 1,6-hexanediol is therefore 35.26 mg/m3/d for workers.

For the DNEL of systemic oral and dermal effects a correction of the starting point is not required, since the NOAEL was derived in a 90–day repeated dose toxicity study (BASF SE, 2014) and equal absorption following dermal and oral up-take is assumed.

According to ECHA guidance R8 and ECETOC Technical Report No 110, the following assessment factors were taken into account for the final DNEL calculation:

- interspecies differences: 4

- intraspecies differences: 5

- exposure duration: 2

-Quality of database: 1

Based on these assessment factors, the DNEL for systemic long-term dermal effects of hexanediol is 400 mg/kg/d / 40 = 10 mg/kg bw/d for workers.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
118
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
LOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General population:  

With one exception only the DNEL for long-term systemic effects is derived since 1,6-hexanediol is non-irritating and acutely practically non-toxic. To be complete an oral acute DNEL was also calculated.

No mortality but clinical symptoms (staggering) are observed in an oral toxicity study in the rat at 2500 mg/kg. A safety factor of 120 (4 (inter species) x 3 (LOAEL to NAEL) x 10 (intra species) ) was taken into consideration, leading to an oral acute DNEL for consumers of 20.8 mg/kg.

For the calculation of the systemic DNELs, the NOAEL of 400 mg/kg/d derived in a 90 -d repeated dose toxicity study was used as starting point:

To correct the interspecies difference between rat and human the observed effect level has to be corrected by the risk assessors 1.15 m3regarding breathing volume and frequency (rats, 24h). Furthermore, since no experimental data is available, as a worst case approach an oral absorption of 50% and absorption following inhalation of 100% is assumed. Thus, the corrected starting point for the general population is 400 / 1.15 mg/m3 /2 = 173.9 mg/m3/d for inhalation. Subsequently the following assessment factors have to be taken into account for the final DNEL calculation:

- intraspecies differences: 10

- exposure duration: 2.

- Quality of database: 1

The DNEL is calculated according to the formula DNEL = (corrected starting point)/(overall AF) as stated in R8 (ECHA, May 2008). Thus, the resulting DNEL for systemic long-term inhalative effects of hexanediol is 8.7 mg/m3/d for the general population.

For the DNEL of systemic oral and dermal effects a correction of the starting point is not required, since the observed effect level was derived in a 90–day repeated dose toxicity study (BASF SE, 2014) and the same absorption is assumes following oral and dermal up-take. The following assessment factors were taken into account for the final DNEL calculation:

- interspecies differences 4

- intraspecies differences 10

- exposure duration: 2

- Quality of database: 1.

The resulting DNEL for systemic long-term oral and dermal effects of hexanediol is therefore 5 mg/kg bw/d for the general population.