Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.1 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):
6
Modified dose descriptor starting point:
NOAEC
Value:
114.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 1000 ppm from a dietary admixture study, which is equivalent to 52 -78 (average 65) mg/kg bw/day for males and 75-161 mg/kg bw/day for females. The corrected 8 hr inhalation NOAEC for workers is NOAEL (65 mg/kg) * 1.76 mg/m3 = 114.6 mg/m3. No factor 2 route extrapolation from oral to inhalation. Kinetic studies indicate a rapid and complete absorption via oral route, and also via inhalation 100% absorption is assumed.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 3 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
DNEL related information
DNEL derivation method:
other: expert judgement
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.5 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):
24
Modified dose descriptor starting point:
NOAEL
Value:
325 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 1000 ppm from a dietary admixture study, equivalent to 65 mg/kg bw/day. Kinetic studies indicate a rapid and complete absorption via oral route, but dermal absorption is maximal 20%. The corrected dermal NOAEL for workers is NOAELoral (65 mg/kg) / 20% = 325 mg/kgbw/day.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 3 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
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

The toxicological profile of p-TSA only indicates a hazard for systemic toxicity following repeated dosing. The NOAEL selection of 65 mg/kg bw/day from a 2-generation study is possibly over-conservative. The only observed effect at the next, 3-times higher, dose level is a small effect on body weight. 90-day studies in rat and dog result to a NOAEL of around 250 mg/kg. However, the Japanese OECD 422 study resulted to a NAOEL of < 120 mg/kg related to an observed slightly thickened urinary bladder epithelium in some of the animals treated at this dose level, which is considered to be reversible and mediated by the peak-dose kinetics following dosing by gavage. All relevant inhalation and dermal exposure scenarios will not lead to similar tubular kidney concentrations causing such effects following the high oral bolus dosing by gavage.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.65 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
56.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 1000 ppm from a dietary admixture study, equivalent to 65 mg/kg bw/day. The corrected 8 hr inhalation NOAEC for workers is NOAEL (65 mg/kg) * 1/1.15 mg/m3 = 56.5 mg/m3. No factor 2 route extrapolation from oral to inhalation. Kinetic studies indicate a rapid and complete absorption via oral route, and also via inhalation 100% absorption is assumed.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.1 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
325 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 1000 ppm from a dietary admixture study, equivalent to 65 mg/kg bw/day. Kinetic studies indicate a rapid and complete absorption via oral route, but dermal absorption is maximal 20%. The corrected dermal NOAEL for general population is NOAELoral (65 mg/kg) / 20% = 325 mg/kgbw/day.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
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

General Population - Hazard via oral 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:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
65 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

These substances are mainly applied in professional or industrial settings. Consequently, consumers/general population will generally not be exposed. The only identified consumer use concerns use as ingredient present (less than 1%) in adhesives/sealants used for gluing textile layers under an iron. This consumer use result to possibly some evaporation of p-TSA available in the sealant. In view of the low vp and the likely incidental consumer use, no significant exposures can be expected. In order to be able to evaluate possible secondary exposures via environment, the long-term systemic DNELs for general population have been derived.