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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
180 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
other: fully documented German MAK value
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 13-week toxicity study by inhalation (6h/day, 5d/week) administration to rats (Hardy, 1988). The starting dose for DNEL calculation was a NOAEC higher than 1442 ppm (5191 mg/m3) for systemic toxicity. The NAEC (8h) derived for workers is 2608 mg/m3 (5191 mg/m3 x 6.7 m3/10 m3 x 6h/8h) after correction for difference between respiratory rates under standard conditions and under conditions of light activity and exposure condition. The application of assessment factors of 2.5 for remaining interspecies differences, 5 for intraspecies differences and 2 for exposure duration from sub-chronic to chronic leads to a DNEL for long-term inhalation exposure - systemic effects higher than 104.3 mg/m3 (29 ppm). It is assumed that the German MAK value of 180 mg/m3 (50 ppm) will be also protective for systemic effects. The MAK commission rational was reported below in the section "Additionnal information - worker".

Therefore, the DNEL of 180 mg/m3 will be used for long-term inhalation exposure - systemic effects.

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:
180 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor:
other: fully documented German MAK value
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
180 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: fully documented German MAK value

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
752.7 mg/kg bw/day
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):
100
Dose descriptor starting point:
NOAEC
Value:
5 191 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
75 270 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on route to route extrapolation from a 13-week toxicity study by inhalation (6h/day, 5d/week) administration to rats (Hardy, 1988). The starting dose for DNEL calculation was a NOAEC higher than 1442 ppm (5191 mg/m3) for systemic toxicity. Considering a ventilation rate of 0.29 m3/kg bw for a 6-hour exposure in rats and a default absorption of 50% by inhalation and 1% by dermal route, the equivalent dermal dose is 75270 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default assessment factor
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

MAK value (Supplement 2006)

No studies of humans have been published which would enable the derivation of a MAK value. The symptoms observed in investigations of eye irritation and acute inhalation toxicity show tetrahydrothiophene to be an  irritant.  At the lowest concentration  of 51 ml/m3 (no information was given in the studies about the number of animals), lacrimation and salivation, the first signs of irritation observed, occurred once in 13 weeks in Sprague-Dawley rats. This does not seem to be significant because of the low frequency. An additional sign of irritation, closing of the eyes, was observed at the next- higher concentration of 236 ml/m3. In another strain of rat (COBS CD BR), no clinical symptoms were seen at a concentration of 125 ml/m3; lacrimation occurred at 234 ml/m3. In the 13-week study with Sprague-Dawley rats, histopathological examination revealed light bleeding in the nasal cavity in one male animal after exposure to a concentration of 1442 ml/m3.

The data demonstrate that Sprague-Dawley rats are more sensitive to exposure to tetrahydrothiophene than are COBS CD BR rats. A concentration of 125 ml/m3 can be considered to be the NOAEC, since no clear irritation was seen in Sprague-Dawley rats after concentrations of 51 ml/m3; the NOAEC for COBS rats was 125 ml/m3. The MAK value has therefore been established at 50 ml/m3. As irritation is the critical effect, the substance is classified in Peak Limitation Category I. Neither substance-specific data nor findings in humans that substantiate at which concentration sensory irritation may be expected are available to establish an excursion factor. Therefore, the basic excursion factor of 1 has been established. Studies which suggest that the substance should be designated with an “Sh” or “Sa” (for substances that cause sensitization of the skin and airways) are not available. In vitro studies did not reveal a genotoxic potential. There are

no studies of the carcinogenicity of tetrahydrothiophene. Classification in a category for carcinogenic substances or germ cell mutagens is therefore not necessary. A study of the developmental toxicity of tetrahydrothiophene in rats with concentrations up to 1910 ml/m3 yielded negative results. As there are no studies with a second species, tetrahydrothiophene is classified in Pregnancy Risk Group D, tending towards C.

MAK value (Supplement 2007)

The  following  study  of  developmental  toxicity  is  described  in  the  2006  MAK documentation.

Groups of 25 female CD rats were exposed to tetrahydrothiophene concentrations of 0, 250, 750 or 2000 ml/m3  for 6 hours a day on gestation days 6 to 15. The analysed concentrations were 0, 234, 782 and 1910 ml/m3. During the exposure period, the symptoms observed in the animals exposed to 234 ml/m3 were licking of the inside of the mouth and lacrimation. The animals exposed to 782 ml/m3 also rubbed their snout and paws on the bottom of the cage and

partially or completely closed their eyes. After exposure to concentrations of 1910 ml/m3, salivation and, towards the end of exposure, extreme agitation were observed in the animals in addition to the above symptoms. A slight reduction in body weight gains was observed in the first few days in the animals of the low exposure group. This reduction was more pronounced in the animals of the medium exposure group during the first four days; water consumption increased progressively. Exposure to 1910 ml/m3 led in these animals also to an initial reduction in food consumption. Tetrahydrothiophene was not found to have any effect on the number of corpora lutea, the number of living foetuses, embryofoetal losses, individual foetal weights or anomalies. The NOAEC for maternal toxicity is therefore 234 ml/m3, the NOAEC for toxic effects on development 1910 ml/m3 (Pennwalt 1988). As the difference between this concentration and the MAK value of 50 ml/m3 is sufficiently large, re-evaluation of the data has allowed the classification of tetrahydrothiophene in Pregnancy Risk Group C.

The MAK-Collection Part I: MAK Value Documentations, Vol. 26. DFG, Deutsche Forschungsgemeinschaft Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32306-7

Supplement 2006: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb11001e0026a/pdf

Supplement 2007: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb11001e0026b/pdf

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.5 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):
50
Dose descriptor starting point:
NOAEC
Value:
5 191 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
926 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 13-week toxicity study by inhalation (6h/day, 5d/week) administration to rats (Hardy, 1988). The starting dose for DNEL calculation was a NOAEC higher than 1442 ppm (5191 mg/m3) for systemic toxicity. The NAEC (24h) derived for general population is 926 mg/m3 (5191 mg/m3 x 6/24 x 5/7) after correction for difference between exposure conditions.

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default assessment factor
AF for interspecies differences (allometric scaling):
1
Justification:
Not needed
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
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:
21 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2
Dose descriptor:
other: German MAK value
AF for intraspecies differences:
2
Justification:
for additional intraspecies differences between workers and the general population
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/m³
DNEL related information
DNEL extrapolated from long term DNEL

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:
DNEL (Derived No Effect Level)
Value:
2.7 mg/kg bw/day
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):
200
Dose descriptor starting point:
NOAEC
Value:
5 191 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
537 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on route to route extrapolation from a 13-week toxicity study by inhalation (6h/day, 5d/week) administration to rats (Hardy, 1988). The starting dose for DNEL calculation was a NOAEC higher than 1442 ppm (5191 mg/m3) for systemic toxicity. Considering a ventilation rate of 0.29 m3/kg bw for a 6-hour exposure in rats and a default absorption of 50% by inhalation and 100% by oral route, the equivalent oral dose is 752.7 mg/kg bw/d for a 5 day/week exposure or 537 mg/kg bw/d for a 7 day/week exposure.

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default assessment factor
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population