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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.14 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
5.51 mg/m³
Explanation for the modification of the dose descriptor starting point:
The relevant dose-descriptor is an oral LOAEL (rat) of 6.25 mg/kg bw/d. -Correction of respiratory volume for relevant duration: For 8h of exposure, the respiratory volume of rats and humans are 0.38 m3/kg bw and 6.7 m3/ person, respectively. The respiratory volume light activity for worker (8h exposure) is 10 m3/person. The correction factor is 1/0.38 x 6.7/10. -Correction for absorption difference between rat and human: No difference in inhalation and oral absorption are expected between rat and human. -Correction for absorption difference between inhalation and oral absorption: The oral absorption is estimated to 50%. According to ECHA Guidance – Chapter R8 (p25), the inhalation absorption is 100% : “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should be assumed”. LOAEC = 6.25 x 1/0.38 x 6.7/10 x 0.5 = 5.51. The corrected LOAEC is 5.51 mg/m3.
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study (103 weeks).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study are considered as a reliable study with a klimish score of 2.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
312.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral LOAEL, rat = 6.25 mg/kg bw/d -Correction for absorption difference between rat and human: No difference in dermal and oral absorption is expected between rat and human. -Correction for absorption difference between dermal and oral absorption: No data on the oral and dermal absorption is available on DETU. According to the REACH guidance a default absorption of 50% is estimated for the oral route. Considering the human dermal absorption of thiourea, an analogue substance to DETU, a dermal absorption of 1% will be used as default value for DETU. Therefore, the corresponding dermal LOAEL is 312.5 mg/kg bw/day (= 6.25 x 50/1).
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study (103 weeks).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study is considered as a reliable study with a klimish score of 2.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Key study for DNEL calculation / Long-term exposure (systemic effects)/ read-across

A 2-year carcinogenicity study on rats and mice is available on DETU by oral route (NCI 1978).

Study was performed to determine whether DETU have the capacity to produce cancer in animals. DETU was administered in diet for 103 weeks at concentrations of 125 and 250 ppm (6.25 and 12.50 mg/kg bw/d, respectively) to rats and 250 and 500 ppm (12.5 and 25 mg/kg bw/d, respectively) to mice.

No mortality, no clinical signs were observed on rats and mice. No change of body weight gain were observed on rats, but a decrease of body weight gain was observed at both doses in mice.

Based upon statistical results, the administration of DETU was associated with the increased incidence of thyroid follicular-cell carcinomas in male rats and thyroid follicular-cell neoplams in female rats (at 125 and 250 ppm).

In mice (in both sexes), the neoplasms observed were similar in type and distribution in dosed and control mice (ex: alveolar/bronchiolar adenoma, hepatocellular adenoma and carcinoma, leukemia or malignant lymphoma...). None of statistical tests for any site revealed a significant positive association between administration of compound and increased tumor incidence.

Under the conditions of the bioassay, DETU was carcinogenic in Fischer 344 rats, inducing thyroid neoplasms and hyperplasia. However, DETU was considered as not carcinogenic in B6C3F1 mice.

The LOAEL for toxicity is 125 ppm (6.25 mg/kg bw/d), based on thyroid toxicity in rats at this dose.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
2.71 mg/m³
Explanation for the modification of the dose descriptor starting point:
The relevant dose-descriptor is an oral LOAEL (rat) of 6.25 mg/kg bw/d. -Correction of respiratory volume for relevant duration: For 24-hr exposition, the respiratory volume of rats is 1.15 m3/kg bw. The correction factor is 1/1.15. -Correction for absorption difference between rat and human: No difference in inhalation and oral absorption are expected between rat and human. -Correction for absorption difference between inhalation and oral absorption: The oral absorption is estimated to 50%. According to ECHA Guidance – Chapter R8 (p25), the inhalation absorption is 100% : “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should be assumed (i.e. factor 1)”.  The corrected LOAEC is 2.71 mg/m3 ( = 6.25 x 1/1.15 x 0.5)
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study (103 weeks).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study are considered as a reliable study with a klimish score of 2.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
312.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The relevant dose-descriptor is an oral LOAEL (rat) of 6.25 mg/kg bw/d.   -Correction for absorption difference between rat and human: No difference in dermal and oral absorption are expected between rats and humans. -Correction for absorption difference between dermal and oral absorption: No data on the oral and dermal absorption is available on DETU. According to the REACH guidance a default absorption of 50% is estimated for the oral route. Considering the human dermal absorption of thiourea, an analogue substance to DETU, a dermal absorption of 1% will be used as default value for DETU. Therefore, the corresponding dermal LOAEL is 312.5 mg/kg bw/day (6.25 x 50/1)  
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study (103 weeks).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on RATs.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study are considered as a reliable study with a klimish score of 2.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
6.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No difference in oral absorption is expected between rat and human.
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study (103 weeks).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on RATs.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population DNELs.
AF for the quality of the whole database:
1
Justification:
The key study are considered as a reliable study with a klimish score of 2.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population