4,4'-bis[4-[bis(2-hydroxyethyl)amino]-6-anilino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

65 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

37 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Systemic Effects:

Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)-amino]stilbene-2,2'disulphonate (CAS 16090 -02 -1) is a technical product which belongs to the category of stilbene fluorescent whitening agents. This substance and all other members of this category do not show acute toxic effects after oral, inhaltory, and dermal administration. They are neither irritant to skin nor eyes, nor genotoxic in-vitro and in-vivo nor sensitzing. In the 28-day subchronic and 24 month chronic toxicity study in the rat, no treatment-related clinical symptoms and no signs of systemic toxicity were observed throughout the study. The only study that showed systemic findings was the two-generation study with bolus dosing of 1000 mg/kg bw. These findings involved the kidneys and this is considered to be related to bolus dosing. For hazard assessment, the two-year feeding study in rats with continous exposure is considered to be most relevant. Since no treatment related adverse effects were observed, the dose level of 791 mg/kg bodyweight per day for females and a dose level of 524 mg/kg bw/day for male is regarded to represent the "no observed adverse effect level" (NOAEL) for this test article and all other category members. The average NOAEL is therefore 658 mg/kg bw/day. The DNELs for inhalation and dermal long-term exposure are derived from the no observed effect level obtained from this oral repeated dose toxicity study with this substance. In general, the calculation of DNEL is based on the observed effect level which has to be modified. To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers: = NOAEL * (1/0.38 m³/kg bw) * 6.7 m³/10 m³* (7/5) (0.38 m³/kg bw: default respiratory volume for the rat corresponding to the daily duration of human exposure. For workers a correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. Since worker are exposed 5 days per week and the rats were exposed 7 days per week a factor 7/5 was included.). Thus, the corrected starting point for workers was 1624.2 mg/m³/d for inhalation. Subsequently other assessment factors are listed, which have to be taken into account for the final DNEL calculation: remaining differences (2.5), intraspecies differences: worker (5). For difference of absorption, a factor of 2 is included. This results in an overall assessment factor of 25. The DNEL for long-term inhalative exposure, systemic effects is therefore 65 mg/m³^.

Corrected starting point for the dermal route for workers: = NOAEL/0.5*(7/5) = 1842.4 mg/kg bw/day (An additional assessment factor (0.5) was used to consider the difference in dermal absorption properties of human and rat skin. Since worker are exposed 5 days per week and the rats were exposed 7 days per week a factor 7/5 was included.). Subsequently, following assessment factors are taken into account for the final DNEL calculation of systemic dermal effects: interspecies differences: human-rat (4), remaining differences (2.5), intraspecies differences: worker (5). This results in an overall assessment factor of 50. The resulting DNEL for long-term dermal systemic effects for the Stilbene fluorescent whitening agents was 37 mg/kg bw/d for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.5 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.6 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

Stilbene fluorescent whitening agents do not show acute toxic effects after oral, inhaltory, and dermal administration. They are neither irritant to skin nor eyes, nor genotoxic in-vitro and in-vivo nor sensitzing. In the 28-day subchronic and 24 month chronic toxicity study in the rat, no treatment-related clinical symptoms and no signs of systemic toxicity were observed throughout the study. Since no treatment related adverse effects were observed a dose level of 791 mg/kg bodyweight per day for females and a dose level of 524 mg/kg bw/day for male is regarded to represent the "no observed adverse effect level" (NOAEL) for this test article and all other category members. The combined NOAEL is therefore 658 mg/kg bw/day. The DNELs for inhalation and dermal long-term exposure are derived from the no observed effect level obtained from this oral repeated dose toxicity study with this substance. In general, the calculation of DNEL is based on the observed effect level which has to be modified. To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for general population: =NOAEL * (1/1.15 m³/kg bw/day) (1.15 m³/kg bw/day: default respiratory volume for the rat corresponding to the daily duration of human exposure. Thus, the corrected starting point for the general population was 572.2 mg/m³ for inhalation. Subsequently other assessment factors are listed, which have to be taken into account for the final DNEL calculation: remaining differences (2.5), intraspecies differences: general population (10). A factor of two is introduced to allow for potential differences in absorption. The DNEL for long-term inhalative exposure, systemic effects is therefore considered to be 11.5 mg/m³.

Corrected starting point for the dermal route for general population: = NOAEL/0.5 = 1316 mg/kg bw/day (An additional assessment factor (0.5) was used to consider the difference in dermal absorption properties of human and rat skin.) Subsequently, following assessment factors are taken into account for the final DNEL calculation of systemic dermal effects: interspecies differences: human-rat (allometric scaling factor of 4), remaining differences (2.5), intraspecies differences: general population (10). The resulting DNEL for long-term dermal systemic effects of stilbene fluorescent whitening agents was 13 mg/kg bw/d for general population.

Corrected starting point for the oral route for general population: = NOAEL = 658 mg/kg bw

Subsequently, following assessment factors are taken into account for the final DNEL calculation of systemic dermal effects: interspecies differences: human-rat (allometric scaling factor of 4), remaining differences (2.5), intraspecies differences: general population (10). The resulting DNEL for long-term oral systemic effects of Stilbene fluorescent whitening agents was 6.6 mg/kg bw/d for general population