Methanesulfonic acid, 1,1'-(1,6-hexanediyldiimino)bis[1-oxo-, sodium salt (1:2)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 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:

245 mg/m³

AF for dose response relationship:

1

Justification:

no additional AF necessary

AF for differences in duration of exposure:

2

Justification:

extrapolation from subchronic animal data to chronic human situation; default value according to REACH guidance documents

AF for interspecies differences (allometric scaling):

1

Justification:

included already in route-to-route extrapolation to derive dose descriptor starting point.

AF for other interspecies differences:

2.5

Justification:

default value according to REACH guidance documents

AF for intraspecies differences:

5

Justification:

default value according to REACH guidance documents

AF for the quality of the whole database:

1

Justification:

no additional AF necessary

AF for remaining uncertainties:

1

Justification:

no additional AF 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

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:

13.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

1 390 mg/kg bw/day

AF for dose response relationship:

1

Justification:

no additional AF necessary

AF for differences in duration of exposure:

2

Justification:

extrapolation from subchronic animal data to chronic human situation; default value according to REACH guidance documents

AF for interspecies differences (allometric scaling):

4

Justification:

extrapolation from rats to humans; default value according to REACH guidance documents

AF for other interspecies differences:

2.5

Justification:

default value according to REACH guidance documents

AF for intraspecies differences:

5

Justification:

default value according to REACH guidance documents

AF for the quality of the whole database:

1

Justification:

no additional AF necessary

AF for remaining uncertainties:

1

Justification:

no additional AF 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

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

PCMS is not irritating to the skin or eye and has no local effects in an acute inhalation study. PCMS is not sensitizing. Consequently local DNELs are not applicable for PCMS.

Long-term DNEL:

The point of departure for systemic toxicity is the comprehensive sub-chronic oral toxicity study in rats. In this study a NOAEL of 278 mg/kg/day was established.

Taking into account the REACH Guidance default assessment factors:

Intraspecies factor rat->humans: 4

Additional uncertainty: 2.5

Interspecies factor for worker: 5

Time-extrapolation sub-chronic-> chronic 2

The overall assessment factor will be 100.

Consequently, the long-term DNEL (worker, oral) will be 2.8 mg/kg/day.

The default absorption values of 50% and 100% are taken for oral and inhalation exposure, respectively. As outlined in the chapter toxicokinetic these values can be considered as conservative.

Dermal absorption is assumed to be low. Based on the “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance” an absorption of 10% was chosen for the DNEL calculation (Footnote page 156).

Taking into account the above mentioned oral (50%) and inhalation (100%) absorption values, the default body weight for worker (70 kg) and a default respiratory volume of 10 m3, the long-term DNEL (worker, inhalation) will be: 10 mg/m3

Taking into account the above mentioned oral (50%) and dermal (10%) absorption values, the long-term DNEL (worker, dermal) will be: 13.9 mg/kg/day.

The available acute toxicity studies in rats indicate low systemic toxicity. PCMS is not irritating to the skin or eye and has no local effects in an acute inhalation study. PCMS is not sensitizing. Consequently, for exposure by inhalation, an acute exposure assessment factor of 2 might be applied to account for potential peak exposure within the day.

PCMS has developmental toxicity properties. In a comprehensive developmental toxicity test in rats a NOAEL for maternal and developmental toxicity of 232 mg/kg/day was established. The point of departure for developmental toxicity is 232 mg/kg/day.

Taking into account the REACH Guidance default assessment factors:

Intraspecies factor rat->humans: 4

Additional uncertainty: 2.5

Interspecies factor for worker: 5

The overall assessment factor will be 50

Consequently, the long-term developmental toxicity DNEL (worker, oral) will be 4.6 mg/kg/day. Since this value is higher than the systemic DNEL (long term, oral) calculated above it is considered that the systemic DNEL covers developmental toxicity and the lowest DNEL should be used for risk assessment.

Short-term DNEL:

The available acute toxicity studies in rats indicate low systemic toxicity. PCMS is not irritating to the skin or eye and has no local effects in an acute inhalation study. PCMS is not sensitizing. Consequently, an acute exposure assessment factor of 2 will be applied to account for potential peak exposure within the day.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

The formulation containing PCMS is a tanning agent, which is used in industrial sites (tannery). The X-Tan formulation contains 35% PCMS as the active ingredient. PCMS hydrolyses rapidly at pH 7 and pH 9 to form the major hydrolysis product, hexamethylene diamine or insoluble poly urea. Hydrolysis is rapid with the hydrolysis half-life of X-Tan measured as 3.5 hours at pH 7 and 10 minutes at pH 9 respectively (see CSR Section 4.1.1.1). X-Tan is used in a buffered process which is regulated at, at least, pH 8 for 18-24 hours. During the industrial use as tanning agent, either X-Tan has reacted with peptide / amino acid of raw hide or X-Tan is completely hydrolysed during tanning process. The wet whites, leathers and waste water after the tanning process have been thoroughly tested. No PCMS / X-Tan can be detected. Therefore, the exposure of PCMS / X-Tan to general public can be excluded. DNELs for the general population are not applicable for X-Tan.