Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
16.18 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
8.13 mg/m³
Explanation for the modification of the dose descriptor starting point:

16.18 mg/m3 x [6.7/10 x 6/8] = 8.13 mg/m3

AF for dose response relationship:
1
Justification:
None required. A clear systemic NOAEC was derived.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from a subacute study to a chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required as taken into account during correction of starting point.
AF for other interspecies differences:
1
Justification:
No remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies variation among workers.
AF for the quality of the whole database:
1
Justification:
None required. The quality of available data is good.
AF for remaining uncertainties:
2.5
Justification:
Default value - any remaining uncertainties.
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:
0.04 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor:
LOAEC
Value:
3 mg/m³
AF for dose response relationship:
3
Justification:
Extrapolation of a NOAEC from a LOAEC.
AF for differences in duration of exposure:
1
Justification:
The factor driving the lung effects is the accumulation of MBTC and/or its decomposition product in the lung due to an overwhelming of the lung clearance, therefore the effect is dose-related but not time-related.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for local effects.
AF for other interspecies differences:
1
Justification:
Not required for repiratory tract corrosion in rodents which have a higher respiration rate and lung SA per kg.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies variation among workers.
AF for the quality of the whole database:
1
Justification:
None required. The quality of available data is good.
AF for remaining uncertainties:
2.5
Justification:
Remaining uncertainties - default value for local effects in the respiratory tract.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

30 x [50/50]  = 30 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear (and conservative) NOEL for maternal toxicity was derived.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default factor in extrapolating from rabbit to man.
AF for other interspecies differences:
1
Justification:
No remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies variation among workers.
AF for the quality of the whole database:
1
Justification:
None required. The quality of available data is good.
AF for remaining uncertainties:
2.5
Justification:
Default value - any remaining uncertainties.
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:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

A 28-day repeat dose inhalation study (GLP compliant, although no guideline cited) and a 90-day repeat dose oral study (OECD 408), inclusive of a screening for reproduction study (OECD 421) are available in rats, along with modern developmental toxicity studies in the rat and rabbit (OECD 414). These studies give no evidence of effects on fertility, although in the rabbit, the No-Observed-Effect Level (NOEL) for maternal toxicity was determined to be 30 mg/kg bw/day based on clinical findings, lower gestation bodyweights, lower bodyweight gain and lower food consumption seen at 120 mg/kg bw/day and aborted pregnancies at 60 and 120 mg/kg bw/day (secondary effects to maternal toxicity). The NOEL for developmental toxicity was determined to be 60 mg/kg bw/day based on increases in post-implantation loss, increases in total and early resorption sites and lower foetal body weights at 120 mg/kg bw/day. The material was not teratogenic in rats or rabbits. The material was otherwise not acutely toxic in acute oral studies, and was not genotoxic in an Ames test, a chromosome aberration assay, or a mammalian cell mutation assay. An in vivo micronucleus assay was also negative. With respect to calculation of systemic DNELs, for each value the route of derivation that gave the most conservative DNEL was used. This was either the repeat dose inhalation study or the rabbit developmental toxicity study for maternal toxicity. Regarding DNELs for WORKERS Skin/Eye irritation, MBTC is proposed to be classified as a corrosive substance and as an irritant to respiratory system. However, it is not possible to derive a DNEL based on the available data. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee “adequately control of risks”, it is necessary to stipulate risk management measures that prevent dermal exposure that cause skin, eye and respiratory irritation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard 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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard 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:
no hazard identified
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

The registered substance will not be made available to the general public and so derivation of the DNEL values for this population group was considered to be inappropriate.