Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20.5 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

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:

53 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 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) is a technical product which belongs to the stilbene fluorescent whitening agents. This substance does not show acute toxic effects after oral and dermal administration. It is not irritant to skin but can cause serious irritation to the eyes. It is neither genotoxic in-vitro and in-vivo nor sensitizing. In a 2 year chronic toxicity / carcinogenicity study in the rat, a pancreatic stimulation effect was observed in the highest dose tested (50000 ppm = 2300 to 2620 mg/kg bw/day). For exposure assessment, the two-year chronic toxicity study in rats with continous exposure is considered to be most relevant. Since no treatment related adverse effects were observed at the mid-dose, the dose level of 226 mg/kg bodyweight per day for females and a dose level of 190 mg/kg bw/day for male is regarded to represent the "no observed adverse effect level" (NOAEL) for this test article. 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/2 * (1/0.38 m³/kg bw) * 6.7 m³/10 m³* (7/5) (For difference of absorption, a factor of 2 is included. 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 234 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). This results in an overall assessment factor of 12.5. The DNEL for long-term inhalative exposure, systemic effects is therefore 18.7 mg/m³.

Corrected starting point for the dermal route for workers: = NOAEL (190 mg/kg b w) /0.1*(7/5) = 2660 mg/kg bw/day

 (An additional assessment factor (0.1) was used because the substance was found to be non permeable to skin (Wollny 1995).

 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).

Duration: 1

Quality: 1

 This results in an overall assessment factor of 50. The resulting DNEL for long-term dermal systemic effects for the test substance is 53 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:

3.4 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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

19 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:

1.9 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

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate) does not show acute toxic effects after oral and dermal administration. It is neither irritant to skin nor genotoxic in-vitro and in-vivo nor sensitizing. In the 2-year combined chronic toxicity / carcinogenicity study in the rat, a pancreatic stimulation effect was observed in the highest dose tested (50000 ppm = 2300 to 2620 mg/kg bw/day). For exposure assessment, the two-year chronic toxicity study in rats with continuous exposure is considered to be most relevant. Since no treatment related adverse effects were observed at the mid-dose, the dose level of 226 mg/kg bodyweight per day for females and a dose level of 190 mg/kg bw/day for male is regarded to represent the "no observed adverse effect level" (NOAEL) for this test article. 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/2*(1/1.15 m³/kg bw/day) (A factor of two is introduced to allow for potential differences in absorption. 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 84.6 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). The DNEL for long-term inhalative exposure, systemic effects is therefore considered to be 3.4 mg/m³.

Corrected starting point for the dermal route for general population: = NOAEL/0.1 = 1900 mg/kg bw/day (An additional assessment factor (0.1) was used to consider the absence of skin permeability observed in the in-vitro study (Wollny 1995) 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 the substance was 19 mg/kg bw/day for general population.

Corrected starting point for the oral route for general population: = NOAEL = 190 mg/kg bw/day. Subsequently, following assessment factors are taken into account for the final DNEL calculation of systemic oral 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 the substance was 1.9 mg/kg bw/d for general population.