Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Technical Report No. 110 Page 62
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEC
Value:
525 mg/m³
Explanation for the modification of the dose descriptor starting point:
Comparable resorption for oral and inhalation routes; Human body weight of 70 kg/person; Daily respiration volume for a worker of 10 mg/m3
AF for dose response relationship:
1
Justification:
A clear dose response relation established in the original study.
AF for differences in duration of exposure:
2
Justification:
The exposure duration did not cover the third trimester of pregnancy.
AF for interspecies differences (allometric scaling):
2.4
Justification:
The allometric scaling factor for rabbit given as 2.4 in ECHA REACH Guidance.
AF for other interspecies differences:
5
Justification:
The number of species investigated is 3 (rabbit, rat and mice), the rabbit being the most sensitive species.
AF for intraspecies differences:
1
Justification:
An informed AF of 1 is proposed when using prenatal data for DNEL derivation.
AF for the quality of the whole database:
1
Justification:
All data are Klimish 1 or 2. Additional AF for the read-across approach is considered to be not necessary, because it can be reasonably assumed that the NOAEL for the target chemical should be higher than that for the source chemical.
AF for remaining uncertainties:
1
Justification:
An informed AF of 1 is proposed; The remaining uncertainties is already ccovered by using AF of 5 for other interspecies 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 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
other: ECETOC (2003) Derivation of Assessment Factors for Human Health Risk Assessment
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Comparable resorption for oral and dermal routes.
AF for dose response relationship:
1
Justification:
A clear dose response relation established in the original study.
AF for differences in duration of exposure:
2
Justification:
The exposure duration did not cover the third trimester of pregnancy.
AF for interspecies differences (allometric scaling):
2.4
Justification:
The allometric scaling factor for rabbit given as 2.4 in ECHA REACH Guidance.
AF for other interspecies differences:
5
Justification:
The number of species investigated is 3 (rabbit, rat and mice), the rabbit being the most sensitive species.
AF for intraspecies differences:
1
Justification:
An informed AF of 1 is proposed when using prenatal data for DNEL derivation.
AF for the quality of the whole database:
1
Justification:
All data are Klimish 1 or 2. Additional AF for the read-across approach is considered to be not necessary, because it can be reasonably assumed that the NOAEL for the target chemical should be higher than that for the source chemical.
AF for remaining uncertainties:
1
Justification:
An informed AF of 1 is proposed; The remaining uncertainties is already covered by using AF of 5 for other interspecies differences.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified. The long-term DNEL concerning reprotoxic (developmental) effects also covers possible acute toxic effects.

Long-term inhalatory systemic DNEL

- based on NOEL (developmental, oral) in rabbits: 75 mg/kg bw/d

- according to the method mentioned in ECETOC Technical Report No. 110


DNEL (inhal.):

= (NOEL(oral, rabbit) /allometric scaling factor) x human body weight / respiration volume (worker) /assessment factor (unborn child)/additional factor (duration)

= (75 mg/kg bw/d /2.4) x 70 kg / 10 m3/ 5 / 2

= 22 mg/m3

with

NOEL(oral, rabbit): 75 mg/kg bw/d

allometric scaling factor (rabbit to human): 2.4

human body weight: 70 kg

respiration volume (worker): 10 m3

assessment factor (unborn child): 5, considering 3 species (rabbit, rat and mouse) investigated

additional factor (duration): 2, considering the shorter exposure duration than the pregnancy of the species

Long-term dermal systemic DNEL

-based on NOEL (developmental, oral) in rabbits: 75 mg/kg bw/d

-according to the method mentioned in the ECETOC Technical Report No. 110


DNEL (dermal)     

= NOEL(oral, rabbit) /allometric scaling factor/assessment factor (unborn child)/additional factor (duration)

= 75 mg/kg bw/d /2.4 / 5 / 2

= 3 mg/kg bw/d

with

NOEL(oral, rabbit): 75 mg/kg bw/d

allometric scaling factor (rabbit to human): 2.4

assessment factor (unborn child): 5, considering 2 species (rabbit and mouse) investigated

additional factor (duration): 2, considering the shorter exposure duration than the pregnancy of the species

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.5 µg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
By inhalation
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:
other toxicological threshold
Value:
1 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
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:
other toxicological threshold
Value:
1 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
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

Use of tetraglyme in consumer product is not supported by the registrant of this dossier. The general population should not be exposed to tetraglyme and a DNEL for the general popublation is not relevant.

Due to the historical reasons the general population exposure may have been occured, however. The threshold values based on the TTC concept provided in this dossier is soley for the purpose of the risk assessment that may have been occured in the past.