Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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:
246 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is a OECD 422 combined 28-day/reproduction screening study with Tosyl chloride which at 150 mg/kg bw showed no systemic toxicity. The corrected 8 hr inhalation NOAEC for workers is NOAEL(150 mg/kg) * 1.76 mg/m3 = 246 mg/m3. No factor 2 route extrapolation from oral to inhalation. Tosyl chloride is rapidly hydrolysed to p-Toluenesulfonic acid which is well absorbed via oral route (>80%). No data are available on absorption via inhalation route, but similar as oral absorption seems reasonable.

AF for dose response relationship:
1
Justification:
No specific concerns.
AF for differences in duration of exposure:
6
Justification:
The guidance indicates that for sub-acute to chronic a factor 6 should be applied, although the animals have been dosed for 36-51 days rather than 28 days. Besides, the effects relate to local irritation in gastro-intestinal system, for which also the threshold for irritation from exposure is not expected to change with duration.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent and valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
Already conservative approach. Available data indicate that the NOAEL for systemic toxicity is higher than the NOAEL used as staring point.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is a OECD 422 combined 28-day/reproduction screening study with Tosyl chloride which at 150 mg/kg bw showed no systemic toxicity. The corrected 8 hr inhalation NOAEC for workers is NOAEL(150 mg/kg) * 1.76 mg/m3 = 246 mg/m3. Direct extrapolation from oral is a conservative approach, as dermal absorption can be expected to be lower than oral absorption.

AF for dose response relationship:
1
Justification:
No specific concerns.
AF for differences in duration of exposure:
6
Justification:
The guidance indicates that for sub-acute to chronic a factor 6 should be applied, although the animals have been dosed for 36-51 days rather than 28 days. Besides, the effects relate to local irritation in gastro-intestinal system, for which also the threshold for irritation from exposure is not expected to change with duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor.
AF for intraspecies differences:
5
Justification:
Default assessment factor.
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent and valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
Already conservative approach. Available data indicate that the NOAEL for systemic toxicity is higher than the NOAEL used as staring point.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high 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

Tosyl chloride is only used as chemical intermediate in industrial settings. Tosyl chloride rapidly hydrolyses to p-Toluenesulfonic acid and HCl, both corrosive acids. The substance itself is irritating to skin and corrosive to the eyes. Furthermore the substance is classified as skin sensitizer category 1. Various oral acute systemic toxicity and repeated dose studies have indicated that its systemic toxicity is low. Consequently the sensitisation and corrosive effects are considered the most relevant for the risk assessment.

In case a substance has been classified as a sensitizing agent, a DNEL or DMEL for sensitization endpoint cannot easily be derived as this may be extremely low and due to intra-individual variations. Therefore a quantitative Risk Assessment is not possible, but a qualitative assessment needs to be carried out. (Practical Guide 15 (ECHA 2012)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population