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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:
1.06 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
26.44 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEChuman= NOAELrat× (1/0.38 m3/kg bw) × (6.7m3/10m3) × (100%/100%) = 15 mg/kg bw/day × 1/0.38 × 6.7/10 × 100/100

AF for dose response relationship:
1
Justification:
A NOAEL was defined
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scalling is required for inhalation
AF for other interspecies differences:
1
Justification:
Addressed by modification of starting point
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Data from target substance supplemented by isomeric read across substance
AF for remaining uncertainties:
2.5
Justification:
default- remaining differences
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:
3 750 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):
100
Dose descriptor starting point:
NOAEL
Value:
15 µg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
375 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAELhuman= NOAELrat× (oral absorption/dermal absorption) = 15 mg/kg bw/day × (100%/0.004%)

AF for dose response relationship:
1
Justification:
A NOAEL was defined
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default – rat to human
AF for other interspecies differences:
1
Justification:
Addressed by modification of the starting point
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Data from target substance supplemented by isomeric read across substance
AF for remaining uncertainties:
2.5
Justification:
default- remaining differences
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

Repeat-dose studies with MOTI (Target substance) and MOTE (Source substance) are available; a Weight of Evidence has been used to take into account all available pieces of information. 

In an oral repeat-dose 90-day study in rats with MOTI (Til et al., 1974) the NOAEL was 300 ppm (15 mg/kg bw/day) based on increased relative kidney weight at the 1000 ppm level (but no indication of kidney damage was revealed by function tests or by any of the urine constituents examined). Slightly increased granularity of the cytoplasm of the epithelial cells of the proximal tubules was noted in the kidney of 1000 ppm males at microscopic examination. This endpoint was used as the starting point for long-term systemic DNELs derivation and is considered protective enough for workers.

In an oral 28-day rat study, slightly decreased growth rate and food intake and increased relative weights of the liver and kidneys was noted in 1500 ppm males dietary level during four weeks was accompanied by very slight changes only (Til et al 1973). Increased relative kidney weights accompanied by histological changes at the higher dose levels were noted in another 90-day rat study, for which the LOAEL was set at 300 ppm, based on increased kidney weight (less than 10%), which was not accompanied by any microscopic change (Til et al 1973). The additional 90-day rat study (Drake 1974) gave a lowest NOAEL value at 20 ppm, based on slightly increased absolute and relative adrenal weights in male rats of the 100- and 500-ppm groups. However, because of major deviations this study is considered not reliable (reliability score 4) and therefore was not taken into consideration for selecting an appropriate starting point. In a 90-day dog study, MOTI administration caused slight anaemia at the top-dose of 1000 ppm; the derived NOAEL was 300 ppm (Til et al., 1973). In addition to these repeated dose studies, a 2-generation rat study is also available, where a single dose of MOTI, 300 ppm, was included (a mixture of MOTI and DOTI, 16.9% and 78.8%, respectively, was tested at three dose level in this same study). In this study the NOAEL for DOTI was again 300 ppm because no effects on fertility and development of offspring was noted. Studies using MOTE as the test substance include two 14-day range-finder studies, and a 90-day rat study in which the NOAEL was determined to be the highest tested dose level of 1250 ppm (82 and 91 mg/kg bw/day for males and females, respectively).

MOTI is not an eye or skin irritant and is neither a skin sensitiser.

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

No DNELs have been derived for general population as exposure does not occur during the lifecycle of the substance.

 

The substance is not used by consumers or professionals and only has manufacture, formulation and industrial uses.

 

The substance is used in the industrial processing of polymers, where it is added as a stabilizer and also as a catalyst/process regulator in the production of polyurethanes or silicones. During the processing of the polymer the substance will be completely used up and as a reactive catalyst the substance is destroyed in the production of polyurethanes or silicones. As such the substance does not exist in the products, therefore in-direct exposure of the general population via releases from the end products are not possible. Indirect exposure of the general population via releases to the environment is also not considered to occur, as the substance is only used in industrial settings where there will be effective waste management processes to prevent release.