3-methyl-2-pent-2-enylcyclopent-2-enone

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.514 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

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

Overall assessment factor (AF):

18

Dose descriptor starting point:

NOAEL

Value:

92.17 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

81.25 mg/m³

Explanation for the modification of the dose descriptor starting point:

inhalation NOAEC = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 92.17 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67 = 81.25 mg/m³

ABSoral-rat=oral absorption rate in rats,

ABSinh-human=inhalation absorption rate in humans.

In a worst case approach the default oral absorption rate of 50% for the rat was used in the calculations (default 0.5/1 according to ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health)

.

AF for dose response relationship:

1

Justification:

NOAEC is chosen as starting point.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).

AF for interspecies differences (allometric scaling):

1

Justification:

AF for allometric scaling already included in starting point derivation method; no further factor required.

AF for other interspecies differences:

1

Justification:

Based on ECETOC, Technical Report No. 110.

AF for intraspecies differences:

3

Justification:

Based on ECETOC, Technical Report No. 110.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.6 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

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

Overall assessment factor (AF):

72

Dose descriptor starting point:

NOAEL

Value:

92.17 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

115.2 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = 92.17 mg/kg bw/day*(1/0.8) = 115.2 mg/kg bw/day

ABSoral-rat = oral absorption rate in rats,

ABSdermal-human = dermal absorption rate in humans = 80% (as estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM))

AF for dose response relationship:

1

Justification:

NOAEL is chosen as starting point.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).

AF for interspecies differences (allometric scaling):

4

Justification:

Based on ECETOC, Technical Report No. 110.

AF for other interspecies differences:

1

Justification:

Based on ECETOC, Technical Report No. 110.

AF for intraspecies differences:

3

Justification:

Based on ECETOC, Technical Report No. 110.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

INHALATION

The long-term systemic inhalation DNEL has been derived from an oral NOAEL of 92.17 mg/kg bw/day obtained from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. After route to route extrapolation by correction for the differences in the respiratory volumes of rats and humans over the relevant assessment period and correction for the differences in the respiratory volumes of humans in rest and during light activity a NOAECcorr of 81.25 mg/m³ has been used as dose descriptor starting point. In compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health” a value of 50% for oral absorption has been included in the calculation. Since respiratory rates depend directly on caloric demand no additional allometric scaling for metabolic differences between rats and humans is required anymore. Additional assessment factors of 6 for the transformation of subacute to subchronic data and of 3 to account for intraspecies differences among workers (based on ECETOC, Technical Report No. 110) were used. In conclusion, a DNEL of 4.514 mg/m³ has been determined.

No acute systemic inhalation DNEL has been derived. The substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, TableE.3-1” the hazard via the inhalation route has to be considered low. No acute acute toxicity was observed after oral and dermal exposure. The acute toxicity after inhalation exposure is therefore also considered to be low and any short-term effects are expected to be caused by the irritating properties. The derivation of an acute DNEL is not recommended, and time scaling is not considered appropriate when the toxic effect is mainly driven by the exposure concentration, as is the case for irritation, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health - Appendix R.8-8 Acute toxicity". In conclusion, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the hazard for the inhalation route has to be considered as low. Due to the well-known irritating characteristics general Risk Management Measures and Operational Conditions (RMMs/OCs) are implemented, and the corresponding use of PPE (incl. appropriate respiratory protection) is mandatory, if inhalation exposure is possible. Therefore, the risk of peak exposures of workers by inhalation is considered to be sufficiently controlled.

Local DNELs for the inhalation route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. The neat substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes in form of the conjunctivae. Therefore, a comparable effect on the mucous membranes of the respiratory tract can be assumed. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the local hazard by respiratory irritation is considered as low. Due to the well-known irritating characteristics, general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate respiratory protection is mandatory, if inhalation exposure is possible. In conclusion, the risk of local effects, both long-term and acute, on the respiratory tract of workers is considered to be sufficiently controlled.

DERMAL

The long-term systemic dermal DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation has been done assuming a dermal absorption rate of 80% which was estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM). Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 115.2 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an additional factor of 6 for transforming subacute into subchronic data and an assessment factor of 3 to account for intraspecies differences among the workers (based on ECETOC, Technical Report No. 110). In conclusion, a DNEL of 1.6 mg/kg bw/day has been derived.

No acute systemic dermal DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the dermal route they are not normally assessed, so the establishment of acute toxicity DNELs for the dermal route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, no data on the long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive an acute DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2). According to “ECHA Guidance on Information requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the hazard via the dermal route has been considered as low. Due to the well-known irritant characteristics general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate gloves is mandatory, if skin contact is possible. In conclusion, the risk of peak exposures of workers via the dermal route is considered to be sufficiently controlled although no DNELs can be derived from irritation studies.

Local DNELs for the dermal route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. According to this guidance DNELs covering local dermal effects can only be derived if route-specific data is available. However, no data on the long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive a local DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2), so the hazard for the dermal route has been considered as low according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”. Due to the well-known irritating characteristics of the substance general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate gloves, is mandatory, if skin contact is possible. In conclusion, the risk of local effects, both long-term and acute, on the skin of workers is considered to be sufficiently controlled, although no DNELs can be derived from irritation studies.

EYES

The neat substance is anticipated to be irritating to the eyes, resulting in the corresponding classification Eye Irrit. 1. According to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the substance is considered to exert a low hazard for the eyes. Due to the well-known irritating characteristics of the substance general RMMs and OCs are implemented, and the corresponding use of PPE including appropriate eye protection in form of chemical goggles is mandatory. In conclusion, the risk for effects on the eyes of workers is considered to be sufficiently controlled.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.336 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

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

Overall assessment factor (AF):

30

Dose descriptor starting point:

NOAEL

Value:

92.17 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

40.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day)*(ABSoral-rat/ABSinh-human) = 92.17 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 40.07  mg/m³.

ABSoral-rat=oral absorption rate in rats

ABSinh-human=inhalation absorption rate in humans

In a worst case approach the default oral absorption rate of 50% for the rat was used in the calculations (default 0.5/1 according to ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health).

AF for dose response relationship:

1

Justification:

NOAEL is chosen as starting point.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).

AF for interspecies differences (allometric scaling):

1

Justification:

AF for allometric scaling already included in starting point derivation method; no further factor required.

AF for other interspecies differences:

1

Justification:

Based on ECETOC, Technical Report No. 110.

AF for intraspecies differences:

5

Justification:

Based on ECETOC, Technical Report No. 110.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.96 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):

120

Dose descriptor starting point:

NOAEL

Value:

92.17 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

115.2 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL=NOAELoral*(ABSoral-rat/ABSdermal-human) = 92.17 mg/kg bw/day*(1/0.8) = 115.2 mg/kg bw/day

ABSoral-rat = oral absorption rate in rats,

ABSdermal-human = dermal absorption rate in humans = 80% (as estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM))

AF for dose response relationship:

1

Justification:

NOAEL is chosen as starting point.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).

AF for interspecies differences (allometric scaling):

4

Justification:

Based on ECETOC, Technical Report No. 110.

AF for other interspecies differences:

1

Justification:

Based on ECETOC, Technical Report No. 110.

AF for intraspecies differences:

5

Justification:

Based on ECETOC, Technical Report No. 110.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low 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:

0.768 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):

120

Modified dose descriptor starting point:

NOAEL

Value:

92.17 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation required, NOAEL derived from oral study. Equal oral absorption is anticipated for rats and humans.

AF for dose response relationship:

1

Justification:

NOAEL is chosen as starting point.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422).

AF for interspecies differences (allometric scaling):

4

Justification:

Based on ECETOC, Technical Report No. 110.

AF for other interspecies differences:

1

Justification:

Based on ECETOC, Technical Report No. 110.

AF for intraspecies differences:

5

Justification:

Based on ECETOC, Technical Report No. 110.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

INHALATION

The long-term systemic inhalation DNEL has been derived from an oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. After route to route extrapolation by correction for the differences in the respiratory volumes of rats and humans over the relevant assessment period for the general public, a NOAECcorr of 40.07 mg/m³ has been used as dose descriptor starting point. In compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health” the default value of 50% for oral absorption has been included in the calculation in a worst case approach. Since respiratory rates depend directly on caloric demand no additional allometric scaling for metabolic differences between rats and humans is required anymore. An additional assessment factor of 5 has been included to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) and another one of 6 for transformation of subacute to chronic data. In conclusion, a DNEL of 1.336 mg/m³ has been determined.

No acute systemic inhalation DNEL has been derived. The substance is classified as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, TableE.3-1” the hazard via the inhalation route has to be considered low. No acute acute toxicity was observed after oral and dermal exposure. The acute toxicity after inhalation exposure is therefore also considered to be low and any short-term effects are expected to be caused by the irritating properties. The derivation of an acute DNEL is not recommended, and time scaling is not considered appropriate when the toxic effect is mainly driven by the exposure concentration, as is the case for irritation, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health - Appendix R.8-8 Acute toxicity". In conclusion, according to "ECHA Guidance on Information Requirements and Chemical Safety Assessment - Part E: Risk Characterisation, Table E.3-1" the hazard for the inhalation route has to be considered low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of peak exposures of consumers by inhalation is considered to be adequately controlled.

Local DNELs for the inhalation route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. The neat substance has to be regarded as irritating to the skin and eyes (Skin Irrit. 2; Eye Irrit. 2), which also comprise mucous membranes in form of the conjunctivae. Therefore, a comparable effect on the mucous membranes of the respiratory tract can be assumed. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the local hazard by respiratory irritation is considered as low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of local effects, both long-term and acute, on the respiratory tract of consumers is considered to be adequately controlled.

DERMAL

The long-term systemic dermal DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation has been done assuming a dermal absorption rate of 80% which was estimated using the Skin Absorption Model (SAM) developed by the Research Institute for Fragrance Material (RIFM). Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 115.2 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an additional factor of 2.5 for other interspecies differences and an assessment factor of 5 to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) as well as an additional factor of 6 for transforming subacute into chronic data. In conclusion, a DNEL of 0.96 mg/kg bw/day has been derived.

No acute systemic dermal DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the dermal route they are not normally assessed, so the establishment of acute toxicity DNELs for peak exposures via the dermal route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, no data on long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive an acute DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2). According to “ECHA Guidance on Information requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the hazard via the dermal route is considered as low. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of peak exposures of consumers via the dermal route is considered to be adequately controlled although no DNELs can be derived from irritation studies.

Local DNELs for the dermal route are not derived in compliance with “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health”. According to this guidance DNELs covering local dermal effects can only be derived if route-specific data is available. However, no data on long-term toxicity via the dermal route is available, and DNELs cannot be derived from irritation studies; hence, there are no results to derive a local DNEL. The neat substance and the concentration contained in the industrially marketed formulations are classified as irritating to the skin (Skin Irrit. 2), so the hazard for the dermal route is considered as low according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of local effects, both long-term and acute, on the skin of consumers is considered to be adequately controlled although no DNELs can be derived from irritation studies.

ORAL

The long-term systemic oral DNEL has also been derived from the oral NOAEL of 92.17 mg/kg bw/day derived from an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD TG 422) in rats. Route to route extrapolation is not required, and in a worst case approach equal oral absorption for rats and humans (absorption of 100% is assumed for the rat) has been anticipated. Hence, as dose descriptor starting point for DNEL derivation a NOAELcorr of 92.17 mg/kg bw/day has been used, followed by allometric scaling for interspecies differences between rats and humans, inclusion of an assessment factor of 5 to account for intraspecies differences in the general population (based on ECETOC, Technical Report No. 110) as well as an additional factor of 6 for transforming subacute into chronic data. In conclusion, a DNEL of 0.7681 mg/kg bw/day has been derived.

No acute systemic oral DNEL has been derived. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health – Appendix R.8-8” a DNEL for acute toxicity should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposures. High peak exposures are usually assessed for the inhalation route only. Although peak exposures in theory may also occur for the oral route they are not normally assessed, so the establishment of acute toxicity DNELs for peak exposures via the oral route appears superfluous. Short-term exposures should normally be assessed using the long-term DNELs. However, there are data from acute toxicity studies via the oral route available; all data indicate a low acute toxicity and LD50 values determined (4300 and approx. 5000 mg/kg bw, for the two studies, respectively) and are well above the threshold for classification of 2000 mg/kg bw according to Regulation (EC) No. 1272/2008 (CLP). Hence, no hazard via the oral route has been identified, the substance is not classified for acute toxicity via the oral route, and the derivation of an acute DNEL is not required. In conclusion, the risk of peak exposures via the oral route is considered to be adequately controlled although no acute DNEL has been derived.

EYES

The neat substance is anticipated to be irritating to the eyes, resulting in the corresponding classification Eye Irrit. 2. According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1” the substance is considered to exert a low hazard for the eyes. The risk for workers in industrial and professional settings is controlled by the implementation of appropriate RMMs and OCs; however, since compliance with RMMs and OCs could not be controlled for the general population, and the use of PPE could not be assumed, the risk for the general population is controlled by limiting the concentration of the substance in consumer products to levels resulting in no hazard or low hazard via the respective routes according to “ECHA Guidance on Information Requirements and Chemical Safety Assessment – Part E: Risk Characterisation, Table E.3-1”, including appropriate labelling, and by establishing appropriate use profiles. In conclusion, the risk of effects on the eyes of consumers is considered to be adequately controlled.