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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
60.6 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
307 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
758 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the chronic oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.


Correction for differences in respiratory volume (workers): 2.63


Correction for differences in bioavailability: 1


Correction for light activity at work: 0.67


Correction for differences between human and experimental exposure conditions (workers): 1.4

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep
AF for differences in duration of exposure:
1
Justification:
Default value for duration extrapolation of a chronic to chronic assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when converting animal oral exposure to human inhalation exposure.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies differences (worker)
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns
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:
86 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):
50
Dose descriptor starting point:
NOAEL
Value:
307 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 298 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the chronic oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.


Correction for differences in respiratory volume (workers): 1


Correction for differences in bioavailability: 10


Correction for light activity at work: 1


Correction for differences between human and experimental expousre conditions (workers): 1.4

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep
AF for differences in duration of exposure:
1
Justification:
Default value for duration extrapolation of a chronic to chronic assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling for rat to human
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies differences (worker)
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns.
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

BHET is metabolized to TA and EG.  TA is not classified according to the criteria of the CLP; therefore based on this criteria, there is no hazard identified following exposure to TA.  However, repeated oral exposure to sublethal doses of EG may lead to oxalate nephrosis (renal destruction by calcium-oxalate crystals) and is therefore considered to be relevant for a STOT classification.  In terms of EG renal toxicity, rats appear to be more resistant than rabbits and less resistant than mice (NTP, 2004), however, different strains of rats may show different sensitivities with more severity and more accumulation of oxalate in the kidneys of Wistar rats than Fisher rats (Cruzan et al., 2004). All sub-chronic and chronic oral studies in rats appear to converge in a NOAEL around 150 mg/kg bw/day (Corley et al, 2008).  Information on EG is considered to be directly applicable to an equivalent molar amount of the EG constituent/metabolite arising from exposure to BHET, wherein 1 mole of BHET provides 2 moles of EG (see TK statement).  Therefore, for the safety assessment of workers for systemic effects following inhalation and/or dermal exposure a chronic BHET NOAEL of 307 mg/kg bw/day is considered.


The CLP self-classification of BHET is STOT RE 2 (oral, kidney).  Systemic acute/short-term effects via any route of exposure are not anticipated.  Additionally, local effects via any route of exposure are not anticipated.


References:


NTP (National Toxicology Program). 2004. NTP-CERHR monograph on the potential human reproductive and developmental effects of ethylene glycol. NTP CERHR MON, (11), pp.1-III36.


Cruzan G, Corley RA, Hard GC, Mertens JJ, McMartin KE, Snellings WM, Gingell R, Deyo JA. 2004. Subchronic toxicity of ethylene glycol in Wistar and F-344 rats related to metabolism and clearance of metabolites. Toxicological Sciences, 81(2), pp.502-511.


Corley RA, Wilson DM, Hard GC, Stebbins KE, Bartels MJ, Soelberg JJ, Dryzga MD, Gingell R, McMartin KE, Snellings WM. 2008. Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity. Toxicology and applied pharmacology, 228(2), pp.165-178.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.7 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:
307 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
267 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the chronic oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.


Correction for differences in respiratory volume (general population): 0.87


Correction for differences in bioavailability: 1


Correction for differences between human and experimnetal exposure conditions (general population): 1

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep
AF for differences in duration of exposure:
1
Justification:
Default value for duration extrapolation of a chronic to chronic assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when converting animal oral exposure to human inhalation exposure.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for intraspecies differences (general population)
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns.
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:
30.7 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:
307 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
3 070 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the chronic oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.


Correction for differences in respiratory volume (general population): 1


Correction for differences in bioavailability: 10


Correction for differences between human and experimental expousre conditions (general population: 1

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep
AF for differences in duration of exposure:
1
Justification:
Default value for duration extrapolation of a chronic to chronic assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling for rat to human
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for intraspecies differences (general population)
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns.
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:
3.07 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
307 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
307 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting NOAEL is based on the chronic oral study, therefore, there no additional correction for differences between human & experimental exposure conditions required.


Correction for differences in respiratory volume general population: 1


Correction for differences in bioavailability: 1


Correction for differences between human and experimental exposure conditions (general population): 1

AF for dose response relationship:
1
Justification:
Substance has low toxicity and dose-response curve is not steep
AF for differences in duration of exposure:
1
Justification:
Default value for duration extrapolation of a chronic to chronic assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling for rat to human
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for intraspecies differences (general population)
AF for the quality of the whole database:
1
Justification:
There are sufficient studies available to indicate data from this study are representative.
AF for remaining uncertainties:
1
Justification:
No data indicating there should be additional concerns.
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

Based on use pattern, manufacture of the BHET, and use of the BHET at industrial sites where the substance will be incorporated into a polymer, no exposure to the general public is anticipated at this time.  The systemic long term exposure DNELs following, inhalation, dermal or oral exposure by the general public are included to ensure unforeseen future users where the general public are exposed is addressed in the safety assessment.


BHET is metabolized to TA and EG.  TA is not classified according to the criteria of the CLP; therefore based on this criteria, there is no hazard identified following exposure to TA.  However, repeated oral exposure to sublethal doses of EG may lead to oxalate nephrosis (renal destruction by calcium-oxalate crystals) and is therefore considered to be relevant for a STOT classification.  In terms of EG renal toxicity, rats appear to be more resistant than rabbits and less resistant than mice (NTP, 2004), however, different strains of rats may show different sensitivities with more severity and more accumulation of oxalate in the kidneys of Wistar rats than Fisher rats (Cruzan et al., 2004). All sub-chronic and chronic oral studies in rats appear to converge in a NOAEL around 150 mg/kg bw/day (Corley et al, 2008).  Information on EG is considered to be directly applicable to an equivalent molar amount of the EG constituent/metabolite arising from exposure to BHET, wherein 1 mole of BHET provides 2 moles of EG (see TK statement).  Therefore, for the safety assessment of workers for systemic effects following inhalation and/or dermal exposure a chronic BHET NOAEL of 307 mg/kg bw/day is considered.


The CLP self-classification of BHET is STOT RE 2 (oral, kidney).  Systemic acute/short-term effects via any route of exposure are not anticipated.  Additionally, local effects via any route of exposure are not anticipated.


References:


NTP (National Toxicology Program). 2004. NTP-CERHR monograph on the potential human reproductive and developmental effects of ethylene glycol. NTP CERHR MON, (11), pp.1-III36.


Cruzan G, Corley RA, Hard GC, Mertens JJ, McMartin KE, Snellings WM, Gingell R, Deyo JA. 2004. Subchronic toxicity of ethylene glycol in Wistar and F-344 rats related to metabolism and clearance of metabolites. Toxicological Sciences, 81(2), pp.502-511.


Corley RA, Wilson DM, Hard GC, Stebbins KE, Bartels MJ, Soelberg JJ, Dryzga MD, Gingell R, McMartin KE, Snellings WM. 2008. Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity. Toxicology and applied pharmacology, 228(2), pp.165-178.