Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
73.16 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: DNEL based on German OEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
292 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: DNEL based on German OEL

Workers - Hazard via dermal route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Although members of the category “pentanols” are reported to occur in nature, they are used mainly in industrial applications. The primary routes of anticipated industrial exposure to the members of the category are via inhalation and skin contact.

Based on the available data 3-methylbutan-1-ol causes irritation to the respiratory tract (STOT SE Cat. 3), skin irritation (Cat. 2) and damage to the eyes (Cat. 1).

   

  

Workers – hazard via inhalation route

 

No valid sub-chronic or chronic animal study by the inhalation route, suitable for DNEL derivation, is available for 3-methylbutan-1-ol or its structurally related isomers.  Nevertheless, in an OECD TG 414 study in Himalayan rabbits conducted with 3-methylbutan-1-ol (CAS No. 123-51-3) local irritation effects were observed. Rabbits were exposed to vapours of 0.5, 2.5 and 10 mg 3-methylbutan-1-ol/L for 6 hours/day on days 7 - 19 of gestation (BG-Chemie 1990; Testing Lab.: BASF AG). As result, a slight but statistically significant retardation of body weight gain was observed in the dams of the highest dose group, while the fetuses did not show any embryo-/fetotoxic or teratogenic findings in all dose groups. In addition, irritation effects to the eyes were evident in the animals of the 10 mg/L air dose group. Thus, the NO(A)EC was 2.5 mg/L air for maternal toxicity based on local irritation effects and probably as secondary effect on body weight reduction and 10 mg/L air for developmental toxicity in rabbits, respectively.

  • The maternal NO(A)EC of 2500 mg/m3appears to be an appropriate point of departure for derivation of a local long-term DNEL. Based on different experimental conditions, the experimental NOAEC is corrected to match 8 h exposure under light activity: 2500 mg/m³ * 6h / 8h * 6.7 m³ / 10 m³ = 1256 mg/m³.
  • No additional factor was deemed necessary for differences in exposure duration. Local irritation was observed in the OECD 414 study at 10 mg/m³. This value matches the RD 50 values obtained in mice in the Alarie assays. It also corresponds well to the acute inhalation study by Scala & Burtis (1973) in rats, rabbits, and guinea pigs, where local irritation was seen at 14 mg/m3. Overall, no worsening of effects over time is expected.
  • The standard factor of 5 was chosen for intraspecies difference.
  • An additional factor of 2.5 was applied for remaining differences.
  • 1256 mg/m³ / 1 (duration) / 5 (intraspecies) / 2.5 (remaining differences) / 1 (database quality) = 100 mg/m³

In 2007, the German MAK Commission determined a scientific OEL for the category of pentanol isomers of 20 ppm (= 73.16 mg/m3) based on local irritation effects observed in subchronic vapour inhalation studies in rats, mice and dogs with the structurally related tertiary alcohol 2-methyl-2- butanol (DFG, 2008). In humans, concentrations of 3-methylbutan-1-ol of 100 – 150 ppm (366 – 549 mg/m3) were reported to be irritating to the respiratory tract (Nelson, 1943).

The German scientific OEL of 20 ppm (73.16 mg/m3) is in the same range as the DNEL for local effects derived following the REACH Guidance R8 from the OECD TG 414 study in rabbits. In view of worker safety and consistency between regulations, the OEL value of 73.16 was chosen as the final DNEL value.

 

To account for short-term effects, the German MAK Commission recommended an excursion factor of 4, resulting in a short-term STEL of 292 mg/m3 (= 80 ppm) which is considered appropriate as short-term DNEL for local and systemic effects.

The human pungency threshold determined for pentan-1 -ol for 3 volunteers was 1600ppm (app. 5000mg/m³), which is significantly abovethe derived short term DNEL. The DNEL is thus considered sufficiently conservative.

 

References

 

ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. November 2012.

 

ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.13: Risk management measures and operational conditions. October 2012.

 

ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Charactersisation. November 2012.

 

ECETOC (2010).Guidance on Assessment Factors to Derive a DNEL. Technical Report No 110. October 2010.

 

DFG (2008). MAK, 44.Lieferung. Pentanol isomers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
13 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
218 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
12.5 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):
80
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to route extrapolation was conducted.
AF for dose response relationship:
1
Justification:
The dose response is considered unremarkable.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration from subchronic (starting route) to chronic (end route) is used.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
No additional factor is required.
AF for intraspecies differences:
10
Justification:
Recommended AF for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The qualitiy of the whole database is considered to be sufficient and uncriritcal.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative, since no systemic effects have been observed. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Although members of the category “pentanols” are reported to occur in nature, they are used mainly in industrial applications. Consumer exposure has to be considered as well. The possible routes of consumer exposure to 3-methylbutan-1-ol are via oral intake, inhalation and skin contact.

Based on the available data 3-methylbutan-1-ol has to be considered as irritating to the respiratory tract (STOT SE Cat. 3 according to Regulation (EC) No 1271/2008), irritation to skin (Cat. 2) and as causing damage to eyes (Cat. 1).

 

General Population – hazard via inhalation route

In 2007, the German MAK Commission determined a scientific OEL for the category of pentanol isomers of 20 ppm (= 73.16 mg/m3) based on local irritation effects observed in subchronic vapour inhalation studies in rats, mice and dogs with the structurally related tertiary alcohol 2-methyl-2-butanol (DFG, 2008). In humans, concentrations of 3 -methylbutan-1-ol of 100 – 150 ppm (366 - 549 mg/m3) were reported to be irritating to the respiratory tract (Nelson, 1943).

The German OEL is regarded to be safe for workers; this value was modified for the consumer. According to the ECHA Guidance, the intraspecies factor differs by 2 between the general population and workers. Also the possible exposure time may be by a factor 3 (8 hrs. vs. 24 hrs) and by a factor 1.4 (5 days/week vs. 7 days/week) longer. Therefore an additional AF of 8.4 is applied to the OEL value of 20 ppm. After correcting the inhalation volume for light work (10 m3/6.7 m3), a DNEL for the general population of 3.55 ppm (13 mg/m3) is derived.

 

The respective short term DNEL for the consumer is calculated from the short term DNEL for the worker of 292 mg/m3correcting for the inhalation volume (10 m3/6.7 m3) and an additional safety factor of 2 (worker to general population) leading to a short term inhalative consumer DNEL of 218 mg/m3. These DNELs cover both systemic and local effects.

 

References

 ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration] -response for human health. November 2012.

 ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.13: Risk management measures and operational conditions. October 2012.

 ECHA (2012). Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Charactersisation. November 2012.

 ECETOC (2010).Guidance on Assessment Factors to Derive a DNEL. Technical Report No 110, October 2010.

 DFG (2008). MAK, 44.Lieferung. Pentanol isomers.