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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:
3.53 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
88.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
No data available on inhalation route; therefore DNEL should be derived from an oral route study.
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for other interspecies differences:
2.5
Justification:
Rat to human
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
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:
0.5 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No data available on dermal route; therefore DNEL should be derived from an oral route study.
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Rat to human
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
6 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
5
Acute/short term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
6 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
5

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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):
200
Modified dose descriptor starting point:
NOAEC
Value:
43.48 mg/m³
Explanation for the modification of the dose descriptor starting point:
No data available on inhalation route; therefore DNEL should be derived from an oral route study.
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for other interspecies differences:
2.5
Justification:
Rat to human
AF for intraspecies differences:
10
Justification:
Consumer
AF for the quality of the whole database:
1
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:
0.25 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No data available on dermal route; therefore DNEL should be derived from an oral route study.
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Rat to human
AF for intraspecies differences:
10
Justification:
Consumer
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
3 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
10
Acute/short term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
3 % in mixture (weight basis)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
10

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Rat to human
AF for intraspecies differences:
10
Justification:
Consumer
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

A.- ACUTE TOXICITY. Systemic effects

Acute exposure is assessed when there is possibility of pick exposure. No pick exposures are likely to occur with this substance. Furthermore, assessment of long term exposure would cover acute exposures.

B.- IRRITATION/ CORROSION

 The substance shows irritancy capability when tested at 92%. However when tested at 30% and 5% is not irritant. Therefore this concentration can be defined as the NOAEL. No inter-species AF is to be applied. For intra-species, an AF of 5 is applied for workers and 10 for consumers.

Therefore the threshold is assumed to be 6% for workers and 3% for consumers (18,2% and 9% respectively for 33% preparation).

 Insufficient information was available from the eye irritation test to determine a dose-relationship or a dose dependency for any irritant or corrosive effects.

 C.- SENSITIZATION

The substance does not exhibited experimental evidence of sensitizing potential.

 D.- MUTAGENICITY/ CARCINOGENICITY

There were no indications of a possible non-threshold mutagenic or tumorigenic response by any exposure route and the experimental results show no positive responses for in vitro/ in vivo mutagenicity assays. Therefore DNELs have not been established either for carcinogenicity nor mutagenicity.

E.- REPEAT DOSE TOXICITY: Systemic effects

Starting point for long-term DNELs derivation is a 90 days repeat dose toxicity study in rats. Duration differencesis set in the REACH guidance as AF = 2 (the assessment factor for extrapolation from subchronic to chronic exposure)

Dose-response related issues

Since the DNEL is to be derived from a from a good quality study, the dose response assessment factor was the default value, AF = 1.

Quality of whole database

The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Dermal exposure

Since no dose descriptor was available from a repeated application dermal toxicity study and dermal exposure is the most probable route of human exposure, it was necessary to derive a corrected dermal NOAEL from the oral NOAEL. The oral dose descriptor was used as the basis for route-to-route extrapolation.

Dermal risk assessment is based on the oral NOAEL of 50 mg/kg/day from the 90 day rat study.

It is commonly assumed that dermal absorption will not exceed oral absorption. However worst case scenario would assume to be 100% dermal absorption.

The following adjustment factors are applied for the identification of the reference DNEL:

(1) for duration adjustment a factor of 2 is used

(2) the allometric scaling factor for the rat is 4;

(3) a default factor of 2.5 accounts for additional interspecies differences;

(4) for intraspecies differences the default factor is 5 for workers and for consumers is 10

 Applying these factors to the oral NOAEL:

DNEL dermal, systemic, chronic worker = 50/100 = 0.5 mg/kg bw/day, (1.515 mg/kg bw/day for 33% preparation)

DNEL dermal, systemic, chronic consumers= 50/200 =0.25mg/kg bw/day (0.75 mg/kg bw/day for 33% preparation)

Oral exposure

Starting point is NOAEL of 50 mg/kg/day from a 90 days rat study. Assuming 100% absorption and the AF described above, critical exposure levels are as follows:

DNEL oral, systemic, chronic general population = 50/200= 0.25 mg/kg/day (0.75 mg/kg bw/day for 33% preparation)

No oral exposure is considered for workers.

Inhalatory exposure

For the chronic inhalation exposure DNELs, the corrected NOAEL was derived as a starting point based on the oral NOAEL of 50 mg/kg bw/day, since no study data were available from long term repeated exposure investigations via the inhalation route. This route is considered of minor concern due to the vapour pressure of the substance.

The total assessment factor for the worker population, long term DNEL inhalation, systemic = 2.5*5*2*1*1 = 25 when the subchronic to chronic factor is included.

The total assessment factor for the general population, long term DNEL inhalation, systemic = 2.5*10*2*1*1 = 50 when the factor for subchronic to chronic exposure is included.

Differences in respiration volumes were assessed for converting the oral dose to an inhalation concentration:

Worker Population - NOAEL of 50 mg/kg/d /0.38m3/kg = 131.6 * [6.7 m3/ 10 m3] = 88.16 mg/m3.

General Population - NOAEL of 50 mg/kg/d /1.15m3/kg = 43.48 mg/m3,

Applying the above explained AF:

DNEL inhalation, systemic, chronic worker population = 88.16 / 25 = 3.53 mg/m3 (10.7 mg/m3 for 33% preparation)

DNEL inhalation, systemic, chronic general population = 43.48 / 50 = 0.87 mg/m3 (2.67 mg/m3 for 33% preparation)

The default absorption percentage 100%, for inhalation has also been used in the calculations.