Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 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
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
100 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point according to ECHA R8 guidance (p.59):
Corrected inhalatory NOEC = Oral NOEL (20 mg/kg bw/d) /1.4 * 70 kg bw / 10 m³/person
=> NOAEC worker = 100 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
For interspecies differences dog vs. human: 1 (according TGD Table R.8-4., already covered by correction of starting point: 1.4 for dog)
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

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:
0.57 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):
35
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of substance specific data, oral and dermal absorption are both assumed to be 100%.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic study
AF for interspecies differences (allometric scaling):
1.4
Justification:
study in dogs
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Repeated dose toxicity study is the basis for the derivation of DNELs:


Study:Repeated dose study (rel 2-key, 13 wks, dog, Worth, 1974)



  • dog, male, female,

  • Subchronic capsule study over 90 days

  • dog: 0 (control), 5, 20 or 80 mg/kg bw/d

  • Effects: NOEL > 20 mg/kg bw/day (male + female dogs)


In all dose groups no treatment related effects on behaviour, survival, hematology, clinical chemistry, histopathology, eyes and bone marrow were observed. Occasional episodes of vomiting in 1/4 females and red blood in the feces of this animal given 80 mg/kg bw/d is regarded to be the physiological response to the treatment with the slightly irritating compound.


Reference: Gibson WE, Gossett FO, Koenig GR, Marroquin F (1974), The toxicity of daily oral doses of o-chlorotoluene in the dog, Toxicology Division Lilly Research Laboratories Study D-4433


 


For comparison, the DNELs were also calculated based on the developmental toxicity study with rats reported in IUCLID section 7. 8.2 (rel 2-key, rat, Huntingdon, 1983).


In this study pregnant Charles River rats were exposed from gestation days 6 to 19 to test material at concentrations of 0, 1, 3, or 9 mg/l air for 6 h. The NOAEC for maternal toxicity was 1.1 mg/L, the NOAEC for teratogenicity 3.1 mg/L.


With the NOAEC of 1.1 mg/L air  the following DNLEs were calculated:



  • inhalation systemic longterm

    • Correction for inhalatory NOAEC: 1.1 mg/L * 6/8 * 6.7m³/10m³ = 0.552 mg/L

    • Interspecies variability (remaining differences): 2.5

    • Intraspezies differences: 5

    • Differences in exposure duration: 6

    • For reliability of dose-response: 1

    • For quality of whole database: 1

    • Overall factor: 75

    • DNEL: 0.00737 mg/L = 7.37 mg/m³



  • dermal systemic longterm

    • Correction for oral/dermal starting point: 1100 mg/m³ * 0.29 m³/kg bw = 319 mg/kg bw/d

    • Allometric scaling: 4

    • Interspecies variability (remaining differences): 2.5

    • Intraspezies differences: 5

    • Differences in exposure duration: 6

    • For reliability of dose-response: 1

    • For quality of whole database: 1

    • Overall factor: 300

    • DNEL: 1.06 mg/kg bw/d




These DNELs are slightly higher than the ones calculated basd on the repeated dose study. Therefore, the DNELs calculated based on the repeated oral study in dogs were selected.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
50
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
50 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point according to ECHA R8 guidance (p.58):
Corrected inhalatory NOEC = Oral NOEL (20 mg/kg bw/d) /1.4 * 70 kg bw / 20 m³/person
=> NOAEC general population = 50 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronis study
AF for interspecies differences (allometric scaling):
1
Justification:
For interspecies differences dog vs. human: 1 (already covered by correction of starting point: 1.4 for dog)
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.286 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):
70
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of substance specific data, oral and dermal absorption are both assumed to be 100%.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic study
AF for interspecies differences (allometric scaling):
1.4
Justification:
study in dogs
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.286 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):
70
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1.4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

For details on derivation of DNELs see section "Additional information - workers". The same studies for DNEL derivation were selected for workers and general population.