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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
6.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Acute/short-term exposure - systemic effects

TAED is of very low acute toxicity by all exposure routes. No lethality occurred after oral or dermal administration of 2000 mg/kg (acute oral LD50 is in the range of 8000 mg/kg bw). At the highest TAED exposure concentration tested for acute inhalation toxicity (2.08 mg/l) no mortality occurred.

As TAED has no acute toxic potential leading to classification and labelling, a DNEL for acute toxicity has not to be established. This is in line with ECHA-guidance on information requirements and chemical safety assessment, Chapter R.8 (2008).

Acute/short-term and long term exposure - local effects

TAED has no skin, eye or respiratory irritation properties, is not a skin sensitizing agent and does not cause any local effects following administration by the oral, dermal or inhalation route. Thus, DNELs for local effects after acute/short-term and long-term exposure do not need to be established. This is in line with ECHA-guidance on information requirements and chemical safety assessment, Chapter R.8 (2008).

Long-term exposure - systemic effects

The only toxicologically relevant effect following repeated oral and dermal administration as well as repeated whole body inhalation of TAED was hepatic centrilobular hypertrophy. Its reversibility was demonstrated in the 90-day oral gavage study. The NOAELs for this effect that have been deduced from the 28-day and 90-day oral rat toxicity study are 200 and 250 mg/kg bw/d, respectively. As in the 90 -day study relative liver weights were still significantly increased in male rats at 250 mg/kgbw/d and a substance relation of the centrilobular hypertrophy seen in some rats at this dose level could not be fully excluded, the conservative NOAEL of 90 mg/kg bw/d was finally deduced. This also represents the systemic NOAEL as the absorption of TAED is close to 100%.

 

TAED when administered dermally to rats once daily for six hours for 90 days at dose levels of 0, 20, 200, and 2000 mg/kg bw/d resulted in minimal centrilobular hypertrophy (cytomegaly) in 8/10 and 4/10 males and females, respectively, at the high-dose only. No other treatment-related findings were noted. Based on the effects in this study the NOEL is equal to or greater than 200 mg/kg bw/d. A NOAEL has not been derived by the study author.

The NOEL is a result of the large spacing factor of 10 between the high and mid dose level. Given that the centrilobular hypertrophy seen in 60 % of the animals dosed at 2000 mg/kg bw/d was of minimal severity and represents an adaptive response which was reversible, an actual NOEL close to 2000 mg/kg bw/d can be assumed and an NOAEL of 2000 mg/kg bw/d can be deduced from this study. This is supported by the theoretical dermal NOAEL of 2093 mg/kg bw/d which can be calculated from the oral NOAEL of 90 mg/kg bw/d taking into account the oral bioavailability of 100 % and the dermal penetration rate of 4.3 % for rat skin.

 

In a subacute inhalation toxicity study no adverse effects were found when 10 male and 10 female Wistar rats were exposed in inhalation chambers to TAED dust for 23 consecutive working days, 5 hours/day, at a mean TAED concentration of 283 mg/m³. 

In a subchronic inhalation study rats were exposed in inhalation chambers to concentrations of TAED dust (< 3.5 µm) up to 99.7 mg/m³ for 6 hours a day, 5 days a week, for 13 weeks. A NOAEL for systemic effects could not be derived from this study as the whole body of the animals was exposed to TAED dust and the oral ingestion of unquantifiable amounts of substance would have occurred due to grooming. Thus, the oral NOAEL from the 90-d repeated dose toxicity study in the rat is used to derive a subchronic inhalation NOAEL.

Teratogenicity was evaluated in groups of rats treated with TAED by gavage at dose levels of 0, 40, 200 and 1000 mg/kg bw/d from day 6 to 15 of pregnancy. No clinical signs, behavioral changes, death or abortion were noted in any group. A dose related significantly lower mean daily food consumption accompanied by decreased body weight gains was seen in the 200 and 1000 mg/kg bw/d groups. Whereas these effects were only present during the first treatment days in the 200 mg/kg bw/d group and had no influence on terminal body weight and fetal weight, they were more pronounced in the 1000 mg/kg bw/d group leading to significantly lower mean body weights from day 10 until the end of pregnancy in the 1000 mg/kg bw/d group. Mean fetal and mean placental weight were significantly decreased and the percentage of skeletal variants was significantly increased at the high dose. Visceral and skeletal malformations or anomalies were not significantly increased at all dose levels in comparison to the controls. The NOEL for maternal toxicity was 40 mg/kg bw/d (based on reduced body weight development and food consumption observed at 200 and 1000 mg/kg bw/d). The study authors did not deduce a NOAEL for maternal toxicity. However, as the effect on food consumption and body weight gain observed at 200 mg/kg bw/d was transient and did not influence fetal development, a NOAEL for maternal toxicity above 40 mg/kg bw/d can be assumed. A comparison of this NOAEL with the NOAEL of 90 mg/kg bw/d derived for the non-pregnant rat in the 90 -d repeated dose toxicity study demonstrates that the pregnant rat and non-pregnant rat have a similar susceptibility. For fetuses the NOEL/NOAEL for developmental toxicity was 200 mg/kg bw/d (based on reduced fetal weight at 1000 mg/kg bw/d) and the NOAEL for teratogenicity was 1000 mg/kg bw/d (based on the absence of visceral and skeletal malformations or anomalies at all dose levels).

 

In a weight of evidence approach it has been shown that TAED is of no concern regarding reproduction toxicity.

 

Based on these data the NOAEL of 2000 mg/kg bw/d from the subchronic dermal study and the NOAEL of 90 mg/kg bw/d from the subchronic oral study are used as starting points for the establishment of the dermal and inhalation DNEL, respectively. The oral NOAEL is converted into a subchronic inhalation NOAEL according to the following formula:

For the worker (assuming a daily exposure for 8 hours):

inhalation NOAEL = oral NOAEL x 1/sRV(rat) x ABSoral-rat/ABSinh-human x sRV(human)/wRV(human)

where:

oral NOAEL = 90 mg/kg bw/d

sRV(rat) = standard respiratory volume (rat) = 0.38 m³/kg (8 h)

ABSoral-rat = oral absorption rate = 100 % (based on toxicokinetic data)

ABSinh-human = inhalation absorption rate = assumed to be 100%.

sRV/wRV(human) = standard respiration volume/working respiration volume (6.7 m³/10 m³)  

Thus, the inhalation NOAEL is 159 mg/m³ for the worker.

The following assessment factors are used for the derivation of the long-term systemic DNELs:

Interspecies             4 (allometric scaling rat -> human*)

                                   2.5 (remaining differences)

Intraspecies             5 (worker)

Exposure duration  2 (subchronic to chronic)

Dose-response       1

Quality of database 1

* not to be applied for inhalation exposure

 

The resulting overall assessment factors and DNELs can be calculated as:

worker (dermal exposure): 2000 mg/kg/d /(4 x 2.5 x 5 x 2 x 1 x 1) = 20 mg/kg/d

worker (inhalation exposure): 159 mg/m³ /(2.5 x 5 x 2 x 1 x 1) = 6.4 mg/m³. 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
75 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Acute/short-term exposure - systemic effects

TAED is of very low acute toxicity by all exposure routes. No lethality occurred after oral or dermal administration of 2000 mg/kg (acute oral LD50 is in the range of 8000 mg/kg bw). At the highest TAED exposure concentration tested for acute inhalation toxicity (2.08 mg/l) no mortality occurred.

As TAED has no acute toxic potential leading to clasification and labelling, a DNEL for acute toxicity has not to be established. This is in line with ECHA-guidance on information requirements and chemical safety assessment, Chapter R.8.

Acute/short-term and acute long term exposure - local effects

TAED has no skin, eye or respiratory irritation properties, is not a skin sensitizing agent and does not cause any local effects following administration by the oral, dermal or inhalation route. Thus, DNELs for local effects after acute/short-term abd long-term exposure do not need to be established.

Long-term exposure - systemic effects

The only toxicologically relevant effect following repeated oral and dermal administration as well as repeated whole body inhalation of TAED was hepatic centrilobular hypertrophy. Its reversibility was demonstrated in the 90-day oral gavage study. The NOAELs for this effect that have been deduced from the 28-day and 90-day oral rat toxicity study are 200 and 250 mg/kg bw/d, respectively. As in the 90 -day study relative liver weights were still significantly increased in male rats at 250 mg/kgbw/d and a substance relation of the centrilobular hypertrophy seen in some rats at this dose level could not be fully excluded, the conservative NOAEL of 90 mg/kg bw/d was finally deduced. This also represents the systemic NOAEL as the absorption of TAED is close to 100%.

 

TAED when administered dermally to rats once daily for six hours over a period of 90 days at dose levels of 0, 20, 200, and 2000 mg/kg bw/d resulted in minimal centrilobular hypertrophy (cytomegaly) in 8/10 and 4/10 males and females, respectively, at the high-dose only. No other treatment-related findings were noted. Based on the effects in this study the NOEL is equal to or greater than 200 mg/kg bw/d. A NOAEL has not been derived by the study author.

The NOEL is a result of the large spacing factor of 10 between the high and mid dose level. Given that the centrilobular hypertrophy seen in 60 % of the animals dosed at 2000 mg/kg bw/d was of minimal severity and represents an adaptive response which was reversible, an actual NOEL close to 2000 mg/kg bw/d can be assumed and an NOAEL of 2000 mg/kg bw/d can be deduced from this study. This is supported by the theoretical dermal NOAEL of 2093 mg/kg bw/d which can be calculated from the oral NOAEL of 90 mg/kg bw/d taking into account the oral bioavailability of 100 % and the dermal penetration rate of 4.3 % for rat skin.

 

In a subacute inhalation toxicity study no adverse effects were found when 10 male and 10 female Wistar rats were exposed in inhalation chambers to TAED dust for 23 consecutive working days, 5 hours/day, at a mean TAED concentration of 283 mg/m³. 

In a subchronic inhalation study rats were exposed in inhalation chambers to concentrations of TAED dust (< 3.5 µm) up to 99.7 mg/m³ for 6 hours a day, 5 days a week, for 13 weeks. A NOAEL for systemic effects could not be derived from this study as the whole body of the animals was exposed to TAED dust and the oral ingestion of unquantifiable amounts of substance would have occurred due to grooming. Thus, the oral NOAEL from the 90-d repeated dose toxicity study in the rat is used to derive a subchronic inhalation NOAEL.

Teratogenicity was evaluated in groups of rats treated with TAED by gavage at dose levels of 0, 40, 200 and 1000 mg/kg bw/d from day 6 to 15 of pregnancy. No clinical signs, behavioral changes, death or abortion were noted in any group. A dose related significantly lower mean daily food consumption accompanied by decreased body weight gains was seen in the 200 and 1000 mg/kg bw/d groups. Whereas these effects were only present during the first treatment days in the 200 mg/kg bw/d group and had no influence on terminal body weight and fetal weight, they were more pronounced in the 1000 mg/kg bw/d group leading to significantly lower mean body weights from day 10 until the end of pregnancy in the 1000 mg/kg bw/d group. Mean fetal and mean placental weight were significantly decreased and the percentage of skeletal variants was significantly increased at the high dose. Visceral and skeletal malformations or anomalies were not significantly increased at all dose levels in comparison to the controls. The NOEL for maternal toxicity was 40 mg/kg bw/d (based on reduced body weight development and food consumption observed at 200 and 1000 mg/kg bw/d).The study authors did not deduce a NOAEL for maternal toxicity. However, as the effect on food consumption and body weight gain observed at 200 mg/kg bw/d was transient and did not influence fetal development, a NOAEL for maternal toxicity above 40 mg/kg bw/d can be assumed. A comparison of this NOAEL with the NOAEL of 90 mg/kg bw/d derived for the non-pregnant rat in the 90 -d repeated dose toxicity study demonstrates that the pregnant rat and non-pregnant rat have a similar susceptibility.For fetuses the NOEL/NOAEL for developmental toxicity was 200 mg/kg bw/d (based on reduced fetal weight at 1000 mg/kg bw/d) and the NOAEL for teratogenicity was 1000 mg/kg bw/d (based on the absence of visceral and skeletal malformations or anomalies at all dose levels).

 

In a weight of evidence approach it has been shown that TAED is of no concern regarding reproduction toxicity.

 

Based on these data the NOAEL of 90 mg/kg bw/d from the subchronic oral toxicity study and the NOAEL of 2000 mg/kg bw/d from the subchronic dermal study are used as starting points for the establishment of the oral, inhalation and dermal DNEL. The oral NOAEL is converted into a subchronic inhalation NOAEL of 3750 mg/m³ according to the following formula:

For the general population (assuming a daily exposure for 30 min*):

inhalation NOAEL = oral NOAEL x 1/sRV(rat) x ABSoral-rat/ABSinh-human

where:

oral NOAEL = 90 mg/kg bw/d

sRV(rat) = standard respiratory volume (rat) = 0.024 m³/kg (0.5 h)

ABSoral-rat = oral absorption rate = 100 % (based on toxicokinetic data)

ABSinh-human = inhalation absorption rate = assumed to be 100%.

* The main use of TAED is in laundry detergents, machine dishwashing powders as well as in bleach boosters. As inhalation exposure during the use of TAED containing products is very short 0.5 h can be taken as a worst case assumption.

The following assessment factors are used for the derivation of the long-term systemic DNELs:

Interspecies               4 (allometric scaling rat -> human*)

                                   2.5 (remaining differences)

Intraspecies            10 (general population)

Exposure duration    2 (subchronic to chronic)

Dose-response         1

Quality of database   1

* not to be applied for inhalation exposure

 

Based on these assessment factors the DNELs are derived asollows:

general population (dermal exposure): 2000 mg/kg bw/d /(4 x 2.5 x 10 x 2 x 1 x 1) = 10 mg/kg bw/d

general population (oral exposure): 90 mg/kg bw/d / (4 x 2.5 x 10 x 2 x 1 x 1) = 0.45 mg/kg bw/d

general population (inhalation exposure): 3750 mg/m³ / (2.5 x 10 x 2 x 1 x 1) = 75 mg/m³.