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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.64 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
123.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012)
AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on administration of test material to the rat for six weeks (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.3 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
7 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Example B.5 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012)
AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on administration of test material to the rat for six weeks (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
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:
301 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
other: EC3 = 18.6 %
AF for differences in duration of exposure:
1
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Long term systemic DNELs are based on the NOAEL of 100 mg/kg bw/day reported following administration of test substance to the rat by gavage for six weeks during a combined repeat dose toxicity study with reproductive/developmental screening (OECD 422). However, exposure of test animals took place on 7 days per week whereas exposure duration is expected to be 5 days per week for human workers. The modified starting points were therefore corrected to give 88 mg/m3 * 7/5 = 123.2 mg/m3 (worker, systemic, inhalation) and 5000 mg/kg bw/day * 7/5 = 7000 mg/kg bw/day (worker, systemic, dermal).

The overall assessment factor applied to the modified starting points was the product of contributions covering dose response: 1; differences in exposure (subacute to chronic): 6; interspecies variation: 1 (inhalation) or 4 (dermal); other interspecies differences: 2.5; intraspecies differences: 5; quality of database: 1; remaining uncertainties: 1. The resulting long term systemic inhalation DNEL for workers is 1.64 mg/m3 and the long term systemic dermal DNEL for workers is 23.3 mg/kg bw/day.

Derivation of short term systemic DNELs for the inhalation and dermal routes is not considered to be necessary for workers. The test material has been determined to have a low vapour pressure (2.8 x 10E-02 Pa at 25 °C) and a high onset boiling point range (156 °C at 101 kPa). As a result, the potential for generation of inhalable forms of the substance is low. Furthermore, acute studies conducted via the oral and dermal routes reported no mortalities, signs of systemic toxicity or abnormalities at necropsy that would lead to classification. It can therefore be concluded that the substance causes no systemic effects under acute exposure conditions.

A long term DNEL for local effects via the dermal route in workers has been derived because the substance is classified as a skin sensitiser (1B) and effects may occur at the site of first contact irrespective of whether the substance is systemically available. The skin sensitisation hazard to the worker is identical in the short term. Physico-chemical properties of the substance (low vapour pressure and high onset boiling point range) mean that the potential for generating inhalable forms is low and the possibility of respiratory sensitisation following dermal exposure to vapours is considered to be covered in the long term and the short term by the local DNELs derived for the dermal route.

In accordance with banding defined in ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (Version 2.0; November 2012), the test item is considered to be a low hazard with respect to the eyes of workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012)
AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on administration of test material to the rat for six weeks (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.3 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Example B.5 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012)
AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on administration of test material to the rat for six weeks (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Value:
301 µg/cm²
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor starting point:
other: EC3 = 18.6%
AF for intraspecies differences:
5

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on administration of test material to the rat for six weeks (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Long term systemic DNELs are based on the NOAEL of 100 mg/kg bw/day reported following administration of test substance to the rat by gavage for six weeks during a combined repeat dose toxicity study with reproductive/developmental screening (OECD 422). The modified starting points were 43.5 mg/m3 (general population, systemic, inhalation) and 5000 mg/kg bw/day (general population, systemic, dermal). Route to route extrapolation was not required when considering oral intake of the test substance by rats and humans; the NOAEL of 100 mg/kg bw/day was therefore used as the starting point for DNEL calculation.

 

The overall assessment factor applied to the modified starting points was the product of contributions covering dose response: 1; differences in exposure (subacute to chronic): 6; interspecies variation: 1 (inhalation) or 4 (dermal or oral); other interspecies differences: 2.5; intraspecies differences: 10; quality of database: 1; remaining uncertainties: 1. The resulting long term systemic inhalation DNEL for the general population is 0.29 mg/m3, the long term systemic dermal DNEL for the general population is 8.3 mg/kg bw/day and the long term systemic oral DNEL for the general population is 0.17 mg/kg bw/day.

 

Derivation of short term systemic DNELs for the inhalation, dermal and oral routes is not considered to be necessary for the general population. The test material has been determined to have a low vapour pressure (2.8 x 10E-02 Pa at 25 °C) and a high onset boiling point range (156 °C at 101 kPa). As a result, the potential for generation of inhalable forms of the substance is low. Furthermore, acute studies conducted via the oral and dermal routes reported no mortalities, signs of systemic toxicity or abnormalities at necropsy that would lead to classification. It can therefore be concluded that the substance causes no systemic effects under acute exposure conditions.

 

A short term DNEL for local effects via the dermal route in consumers has been derived because the substance is classified as a skin sensitiser (1B) and effects may occur at the site of first contact irrespective of whether the substance is systemically available. The skin sensitisation hazard to the consumer is identical in the long term although prolonged contact with the substance is not intended or envisaged. Physico-chemical properties of the substance (low vapour pressure and high onset boiling point range) mean that the potential for generating inhalable forms is low and the possibility of respiratory sensitisation following dermal exposure to vapours is considered to be covered in the long term and the short term by the local DNELs derived for the dermal route.

 

In accordance with banding defined in ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (Version 2.0; November 2012), the test item is considered to be a low hazard to the eyes of the general population.