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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.145 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
0.52 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1.814 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a sub-chronic toxicity study in dogs (OECD 452). To convert the dog oral NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure, the NOAEL has to be corrected as follows:

Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVdog) × (ABSoral-dog ÷ ABSinh-human) × (sRVhuman ÷ wRV) × (Fstudy ÷ Fworker)

= 0.52 mg/kg bw/day × (1 ÷ 0.134 m³/kg bw) × (1 ÷ 2) × (6.7 m³ ÷ 10 m³) × (7 ÷ 5) = 0.145 mg/m³

sRV = standard respiratory volume; wRV = respiratory volume light activity for worker (8 h); ABS = absorption; Fstudy = frequency of exposure in study; Fworker = frequency of exposure worker

Route-to-route extrapolation within the Beagle dog was based on the respiratory volume of 0.3 L/min/kg bw, leading to an inhalation volume of 0.134 m³/kg bw for a time period of 8 hours, reflecting the normal duration of an 8-hour work shift. The resulting air concentration has been corrected by a factor of 0.67 considering the ratio of the normal inhalation volume of 6.7 m³/person over 8 hours and the increased inhalation volume of 10 m³/person of workers during light activity at work. Moreover, the NOAEL was corrected for the differences in the experimental and human exposure conditions. The animals (dog) were exposed to the test substance 7 days/week, whereas workers are in general exposed 5 days/week (factor 7 days/5 days).

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.

Thus, the corrected starting point for workers is 0.145 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study peformed in dogs over a time period of 1 year.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not applicable for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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:
0.833 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on a dermal NOAEL observed in a repeated dose toxicity study in rats (OECD 410). The frequency of treatment in the dermal repeated dose toxicity study was 5 days/week for the first three weeks and 7 days/week thereafter for 6 h. As the animals were mainly exposed 5 days/week, the frequency of exposure is identical to the exposure frequnency of the worker and no correction factor for the frequency was applied. Therefore, no modification of the dose descriptor starting point is neccessary. An AF of 6 for the conversion of the subacute study to a chronic exposure, an AF of 10 (2.5 x 4) to correct for interspecies differences between rat and man, followed by a factor of 5 to cover for individual variations among the workers were applied.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.024 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
Dose descriptor starting point:
NOAEL
Value:
0.52 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
0.605 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/0.43 m³/kg bw/day (24h)) *(ABSoral-rat/ABSinh-human) = 0.52 mg/kg bw/day*(1/0.43 m³/kg bw/day)*(1/2) = 0.605 mg/m³.

ABS(oral/rat) = oral absorption rate in rats, ABS(inh./human) = inhalation absorption rate in humans

Starting point for the DNEL derivation is the human NAEC for inhalation exposure over 24 hours of 0.605 mg/m³. This value is based on the conversion of the chronic oral NOAEL of 0.52 mg/kg bw/day for dogs from the 1-year study to the corresponding air concentration over a period of 24 hours. Route-to-route extrapolation within the Beagle dog was based on the respiratory volume of 0.3 L/min/kg bw, leading to an inhalation volume of 0.43 m³/kg bw for a time period of 24 hours, reflecting continuous exposure via the environment. As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.

An assessment factor 10 was included to take care of possible intraspecies differences within the general population and an assessment factor of 2.5 for other interspecies differences was considered. However, the substance is not intended for use by the general population, therefore exposure is unlikely.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not classified for acute inhalation toxicity according to Regulation (EC) No 1272/2008.

Short-term high exposures are considered unlikely given the levels of control in place at sites producing

and using the substance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.298 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
178.57 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on a dermal NOAEL observed in a repeated dose toxicity study

in rats (OECD 410). As the frequency of treatment in this study was predominantly 5 days/week, and the exposure frequency of the general population is 7 days/week, the dose descriptor starting point is modified with the factor 5/7 to 178.57 mg/kg bw/day.

An AF of 6 for the conversion of the subacute study to a chronic exposure, an AF

of 10 (2.5 x 4) to correct for interspecies differences between rat and man, followed by a factor of 10 to

cover for individual variations among the workers were applied.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.017 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):
35
Dose descriptor starting point:
NOAEL
Value:
0.52 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.52
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a chronic toxicity study in dogs (OECD 452).

As the frequency of treatment in the study (7 days/week) was identical to the exposure frequency of the general population no correction factor for the frequency was applied. Therefore, no modification of the dose descriptor starting point is necessary.

Further, there is no route-to-route extrapolation necessary.

Starting point for the DNEL derivation is the chronic oral NOAEL of 0.52 mg/kg bw/day from the 1-year study in dogs as most sensitive species. An assessment factor (AF) of 1.4 is included for correction of interspecies differences between dogs and humans, an AF of 2.5 for other interspecies differences and a factor of 10 to consider possible intraspecies differences within the general human population. However, the substance is not intended for use by the general population, therefore exposure is unlikely.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The experimental animal was the dog.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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