Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.5 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:

1 763.15 mg/m³

Explanation for the modification of the dose descriptor starting point:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Worker:

Based on the available data, Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide (Kerocom FM 38), has to be considered as posing the risk of serious damage to the eye (R41; Cat. 1), as potentially skin sensitizing (R43; Cat. 1B), and also has a weak skin irritation potential (R38, no classification according to CLP), respectively.

The primary routes of anticipated industrial and professional exposure of Kerocom FM 38, are via inhalation and skin contact. In industrial settings, ingestion is not an anticipated route of exposure, but has to be considered for the general population (see below).

Dermal short-term and long-term exposure – local and systemic effects:

The substance causes skin sensitization in experimental animals.

For these effects, a qualitative assessment was conducted:

Though sensitization reactions of the skin are generally regarded as threshold effect, deriving a threshold and setting a DNEL is very difficult in practice. As there are only worker uses reported where exposure can be minimized by the appropriate risk management measures and operational conditions, a qualitative assessment was regarded as the most appropriate. Therefore the use of gloves and the use of stringent risk management measures as outlined in ECHA guidance document Part E: Risk Characterization (Table E. 3-1, page 28-32) is required in order to prevent any skin contact with the test substance and thus the occurrence of skin sensitization.

The use of gloves and of stringent risk management measures will also protect the worker from any systemic dermal effects, short-term and long-term.

Professional workers can come in contact with the substance via fuel and lubricants. As the substance is only a weak to moderate skin sensitizer and present in fuel at concentrations well below the threshold for classification & labeling of 1 % for Cat. 1B skin sensitizers, the hazard for professional workers is negligible also taking into account that the use of gloves will prevent any occurrence of skin contact.

 

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats.

This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 1763.15 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account (Escher and Mangelsdorf, 2009; Batke et al, 2011; Bitsch et al, 2006).

- Intraspecies factor: 5 (ECHA Guidance)

- Exposure duration: 6 (ECHA Guidance)

- Remaining differences: 2.5 (ECHA Guidance)

- Dose-response: 1

Total AF = 1 x 5 x 6 x 2.5 x 1 = 75

Based on this calculation the resulting DNEL is 23.5 mg/m³.

- Batke M, Escher S, Hoffmann-Doerr S, Melber C, Messinger H, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.

 

- Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247-S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.

 

 - Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.

-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.

-ECHA: REACh Guidance document R.8

-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.

-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs.Technical Report No. 110, October 2010.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.79 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:

869.56 mg/m³

Explanation for the modification of the dose descriptor starting point:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

Justification:

See Discussion

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:

1.66 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:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see discussion

Justification:

see discussion

Justification:

see discussion

Justification:

see discussion

Justification:

see discussion

Justification:

see discussion

Justification:

see discussion

Justification:

see discussion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.66 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:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Justification:

See discussion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Consumer

Based on the available data, Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide (Kerocom FM 38), has to be considered as posing the risk of serious damage to the eye (R41; Cat. 1), as potentially skin sensitizing (R43; Cat. 1B), and also has a weak skin irritation potential (R38, no classification according to CLP), respectively.

For the general population, all three possible routes of exposure (oral, dermal, inhalation) have to be taken into account.

Dermal short-term and long-term exposure – local effects:

Consumers can come in contact with the substance via fuel and lubricants. As the substance is only a weak to moderate skin sensitizer and present in consumer products well below the threshold for classification & labeling of 1 % for Cat. 1B skin sensitizers, the hazard for consumers is negligible.

Dermal long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term dermal exposure. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats.

The NOAEL of 1000 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. As some dermal uptake is evident (the substance is a skin sensitizer), no correction for differences between oral and dermal uptake was made although dermal uptake is assumed to be lower than oral uptake (see toxicokinetic assessment). Subsequently, the following assessment factors are taken into account for the final DNEL calculation for the oral route: interspecies differences (4), remaining differences (2.5), intraspecies differences (10), exposure duration (6) (AF = 4 x 2.5 x 10 x 6 x 1 x 1 = 600).

As a consequence, the resulting DNEL for long-term dermal systemic effects is 1.66 mg/kg bw/d for the general population.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 4 (ECHA Guidance)

- Intraspecies factor: 10 (ECHA Guidance)

- Remaining differences: 2.5 (ECHA Guidance)

- Exposure duration: 6 (ECHA Guidance)

- Dose-response: 1

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats.

This point of departure was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/d). The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 869.56 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account (Escher and Mangelsdorf, 2009; Batke et al, 2011; Bitsch et al, 2006).

- Intraspecies factor: 10 (ECHA Guidance)

- Remaining differences: 2.5

- Exposure duration: 6 (Batke et.al., 2011)

- Dose-response: 1

Total AF = 1 x 10 x 2.5 x 6 x 1= 150

Based on this calculation the resulting DNEL is 5.79 mg/m³.

Oral long-term exposure – systemic effects:

The NOAEL from an oral repeated dose study with rats conducted according to OECD TG 407 (BASF, 2009) was identified as the appropriate starting point for DNEL derivation for long-term oral exposure. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats.

The NOAEL of 1000 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. Subsequently, the following assessment factors are taken into account for the final DNEL calculation for the oral route: interspecies differences (4), remaining differences (2.5), intraspecies differences (10), exposure duration (6) (AF = 4 x 10 x 2.5 x 6 x 1 x 1 = 600).

As a consequence, the resulting DNEL for long-term oral systemic effects is 1.66 mg/kg bw/d for the general population.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 4 (ECHA Guidance)

- Intraspecies factor: 10 (ECHA Guidance

- Remaining differences: 2.5 (ECHA Guidance)

- Exposure duration: 6 (ECHA Guidance)

- Dose-response: 1

- Batke M, Escher S, Hoffmann-Doerr S, Melber C, Messinger H, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.

- Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247 -S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.

 

- Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.

-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.

-ECHA (2008). REACh Guidance document R.8

-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.

-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs.Technical Report No. 110, October 2010.