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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
168 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: See justification and comments and discussion section below for details.
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC
DNEL value:
502 mg/m³
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
See discussion below.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation study.
AF for other interspecies differences:
1
Justification:
Not required according to ECETOC Technical Reports #86 and #110
AF for intraspecies differences:
3
Justification:
Scientifically justified according to ECETOC Technical Reports #86 and #110
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: See justification and comments
Overall assessment factor (AF):
9
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
Default LOAEL to NOAEL extrapolation factor
AF for differences in duration of exposure:
1
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation route.
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
3
Justification:
see discussion below
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
no hazard identified
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

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 

The available toxicokinetic study on the structural analogue of monopropylene glycol, tripropylene glycol, indicated an oral absorption of at least 86% of the total administered dose. As monopropropylene glycol has a significantly lower molecular weight, its absorption from the gut is expected to occur even faster. Toxicokinetic behavior of monopropylene glycol in humans and experimental animals was also evaluated by the NTP CERHR expert panel (National Toxicology Program, 2004a), which concluded that available data indicate rapid and extensive absorption. Therefore a value of 100% for oral absorption shall be used for risk assessment for monopropylene glycol.

Regarding dermal absorption, an available in vitro study indicated 0.14% dermal absorption, using an infinite exposure. Based on the results of the study, a value of 40% for dermal absorption has been chosen by expert judgment to be used in the risk assessment. This value has been chosen as an average value between the percentage of dermal absorption obtained in the study and the maximal oral absorption (corresponding to 100%), and is considered to represent a worst-case approach. 

Acute toxicity

Monopropylene glycol is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.

Monopropylene glycol is not irritating to the skin and eyes and is not sensitising to the skin. Therefore, no DNELs are derived for these endpoints.

Long-term toxicity

 

Regarding repeated dose toxicity, a NOAEL of 1700 mg/kg bw/day was established in a chronic oral toxicity study with rats (Gaunt, 1972), corresponding to the highest tested dose. In the subchronic inhalation toxicity study with rats, reported by Suber, 1989, a LOAEC of 160 mg/m3 was established for local effects, based on the reported nasal hemorrhaging and ocular discharge in all test groups, while a NOAEC of 1000 mg/m3 was established, based on the decreased body weights of the high dose females. Long-term toxicity of monopropylene glycol by dermal route of exposure was assessed in the study of Stenbäck et al. (1974) of limited reliability with mice, treated twice a week with 0.02 ml of either neat monopropylene glycol or its 50% or 10% solution in acetone. The authors concluded that no substance-caused increase in tumor evidence was evidenced in any group; however, no further data on toxicity are presented. T his information is not sufficient for DNEL derivation, thus a route-to route extrapolation from the available oral toxicity data needs to be performed. However, as no effects were observed at the highest tested dose in the available chronic oral toxicity study, the DNEL for dermal route of exposure is considered to be not quantifiable and will not be derived.

Monoropylene glycol is assessed to be non-mutagenic and not carcinogenic. Based on this, no separate risk characterisation for mutagenicity and carcinogenicity is needed.

Monopropylene glycol did not cause effects on development or fertility in the continuous breeding study with mice administered the test substance in drinking water (Morrissey, 1989) and in the prenatal developmental toxicity study with mice (Bushy Run Research Center, 1993). The NOAEL for reproductive and developmental effects were set at 10100 and 10400 mg/kg bw/day. As these values are well above the NOAEL for repeated dose toxicity, no separate risk assessment for reproductive and developmental toxicity of monopropylene glycol needs to be performed.

  

DNEL calculation

The DNELs are derived using the scientifically based assessment factors as reported by ECETOC (2003).

Long term – inhalation, systemic effects

 

Description

Value

Remark

 

Step 1) Relevant dose-descriptor

NOAEL: 1000 mg/m3

Based on the decreased body weights of high dose females

 

Step 2) Modification of starting point

6/8

 

 

 

 

6.7 m3/10 m3

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

 Correction for activity driven differences of respiratory volumes in active workers compared to workers in rest (6.7 m3/10 m3).

 

Step 3) Assessment factors

 

 

 

Interspecies

1

No allometric scaling is required in case of inhalation exposure

 

Intraspecies

3

The default assessment factor for workers, as proposed by ECETOC

 

Exposure duration

1

No correction for exposure duration has been applied, as available long-term oral toxicity studies indicate no adverse effects at the highest dose levels in case of chronic exposure. As oral absorption is expected to be much higher than inhalation absorption based on the available toxicokinetic data, the introduction of the additional assessment factor for the exposure duration is considered to be not warranted.

 

Dose response

1

 

 

Quality of database

1

 

 

DNEL

Value

 

1000 x (6/8) x (6.7/10) / (1 x 3 x 1) = 168 mg/m3

Long term – inhalation, local effects*

 

Description

Value

Remark

 

Step 1) Relevant dose-descriptor

LOAEL: 160 mg/m3

Based on the reported nasal haemorrhaging and occular discharge at all dose levels

 

Step 2) Modification of starting point

none

 

Correction for exposure duration and

correction for activity driven differences of respiratory volumes in active workers compared to workers in rest are not considered necessary as local effects on the respiratory tract will mainly depend on concentration of the substance in the air and not on duration of exposure nor on the tidal volume 

 

Step 3) Assessment factors

 

 

 

Interspecies

1

No allometric scaling is needed in case of inhalation exposure or local effects

 

Intraspecies

3

The default assessment factor for workers, as proposed by ECETOC

 

Exposure duration

1

Correction for exposure duration from a 90 day exposure to chronic exposure is not considered necessary, as the critical effects (nose bleeding) were reversible over the weekend when animals were not exposed.

 

Dose response

3

extrapolation of LOAEC to NOAEC

 

Quality of database

1

 

 

DNEL

Value

 

160 / (1 x 3 x 1 x 3) = 18 mg/m3

* The obtained DNEL of 18 mg/m3 is higher than the limit concentration of 10 mg/m3 established for aerosols by AIHA. Therefore the latter value shall be regarded as a DNEL for local effects, as it has been established by credible authoritative body, is lower than the calculated DNEL and is adopted by industry.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: See discussion below.
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
DNEL value:
250 mg/m³
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
See discussion below.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation study.
AF for other interspecies differences:
1
Justification:
Not required according to ECETOC Technical Reports #86 and #110
AF for intraspecies differences:
5
Justification:
Scientifically justified according to ECETOC Technical Reports #86 and #110
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: See discussion section below for details.
Overall assessment factor (AF):
15
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
Default LOAEL to NOAEL extrapolation factor
AF for differences in duration of exposure:
1
Justification:
See discussion below
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for inhalation route.
AF for other interspecies differences:
1
Justification:
See discussion below
AF for intraspecies differences:
5
Justification:
See discussion below
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
no hazard identified
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. 

The available toxicokinetic study on the structural analogue of monopropylene glycol, tripropylene glycol, indicated an oral absorption of at least 86% of the total administered dose. As monopropropylene glycol has a significantly lower molecular weight, its absorption from the gut is expected to occur even faster. Toxicokinetic behavior of monopropylene glycol in humans and experimental animals was also evaluated by the NTP CERHR expert panel (National Toxicology Program, 2004a), which concluded that available data indicate rapid and extensive absorption. Therefore a value of 100% for oral absorption shall be used for risk assessment for monopropylene glycol.

Regarding dermal absorption, an available in vitro study indicated 0.14% dermal absorption, using an infinite exposure.Based on the results of the study, a value of 40% for dermal absorption has been chosen by expert judgment to be used in the risk assessment. This value has been chosen as an average value between the percentage of dermal absorption obtained in the study and the maximal oral absorption (corresponding to 100%), and is considered to represent a worst-case approach. 

Acute toxicity

Monopropylene glycol is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.

Monopropylene glycol is not irritating to the skin and eyes and is not sensitising to the skin. Therefore, no DNELs are derived for these endpoints.

Long-term toxicity

 

Regarding repeated dose toxicity, a NOAEL of 1700 mg/kg bw/day was established in a chronic oral toxicity study with rats (Gaunt, 1972), corresponding to the highest tested dose. As no adverse effects were observed at the highest tested dose, DNEL for oral route of exposure is considered to be not quantifiable and will not be derived. In the subchronic inhalation toxicity study with rats, reported by Suber, 1989, a LOAEC of 160 mg/m3 was established for local effects, based on the reported nasal hemorrhaging and ocular discharge in all test groups, while a NOAEC of 1000 mg/m3 was established, based on the decreased body weights of the high dose females. Long-term toxicity of monopropylene glycol by dermal route of exposure was assessed in the study of Stenbäck et al. (1974) of limited reliability with mice, treated twice a week with 0.02 ml of either neat monopropylene glycol or its 50% or 10% solution in acetone. The authors concluded that no substance-caused increase in tumor evidence was evidenced in any group; however, no further data on toxicity are presented. This information is not sufficient for DNEL derivation, thus a route-to route extrapolation from the available oral toxicity data needs to be performed. However, as no effects were observed at the highest tested dose in the available chronic oral toxicity study, the DNEL for dermal route of exposure is also considered to be not quantifiable and will not be derived.

Monoropylene glycol is assessed to be non-mutagenic and not carcinogenic. Based on this, no separate risk characterisation for mutagenicity and carcinogenicity is needed.

Monopropylene glycol did not cause effects on development or fertility in the continuous breeding study with mice administered the test substance in drinking water (Morrissey, 1989) and in the prenatal developmental toxicity study with mice (Bushy Run Research Center, 1993). The NOAEL for reproductive and developmental effects were set at 10100 and 10400 mg/kg bw/day. As these values are well above the NOAEL for repeated dose toxicity, no separate risk assessment for reproductive and developmental toxicity of monopropylene glycol needs to be performed.

 

DNEL calculation

The DNELs are derived using the scientifically based assessment factors as reported by ECETOC (2003).

Long term – inhalation, systemic effects

 

Description

Value

Remark

 

Step 1) Relevant dose-descriptor

NOAEL: 1000 mg/m3

Based on the decreased body weights of high dose females

 

Step 2) Modification of starting point

6/24

 

 

 

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default general population exposure (24 hrs/day, 7 days/week);

 

Step 3) Assessment factors

 

 

 

Interspecies

1

No allometric scaling is required in case of inhalation exposure

 

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

 

Exposure duration

1

No correction for exposure duration has been applied, as available long-term oral toxicity studies indicate no adverse effects at the highest dose levels in case of chronic exposure. As oral absorption is expected to be much higher than inhalation absorption based on the available toxicokinetic data, the introduction of the additional assessment factor for the exposure duration is considered to be not warranted.

 

Dose response

1

 

 

Quality of database

1

 

 

DNEL

Value

 

1000 x (6/24) / (1 x 5 x 1) = 50 mg/m3

Long term – inhalation, local effects*

 

Description

Value

Remark

 

Step 1) Relevant dose-descriptor

LOAEL: 160 mg/m3

Based on the reported nasal haemorrhaging and occular discharge at all dose levels

 

Step 2) Modification of starting point

none

 

Correction for exposure duration and

correction for activity driven differences of respiratory volumes in active workers compared to workers in rest are not considered necessary as local effects on the respiratory tract will mainly depend on concentration of the substance in the air and not on duration of exposure nor on the tidal volume 

 

Step 3) Assessment factors

 

 

 

Interspecies

1

No allometric scaling is needed in case of inhalation exposure or local effects

 

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

 

Exposure duration

1

Correction for exposure duration from a 90 day exposure to chronic exposure is not considered necessary, as the critical effects (nose bleeding) were reversible over the weekend when animals were not exposed.

 

Dose response

3

extrapolation of LOAEC to NOAEC

 

Quality of database

1

 

 

DNEL

Value

 

160 / (1 x 5 x 1 x 3) = 11 mg/m3

* The obtained DNEL of 11 mg/m3 is higher than the limit concentration of 10 mg/m3 for workers exposure established for aerosols by AIHA. Therefore the latter value shall be regarded as a DNEL for local effects for general population, as it has been established by credible authoritative body, is lower than the calculated DNEL and is considered to be sufficient to protect both workers and general population.