Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
79.34 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA factors in combination with recent scientific literature
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2 380 mg/m³
Explanation for the modification of the dose descriptor starting point:

Key oral OECD 422 toxicity study available; no repeated dose inhalation toxicity study available.

AF for dose response relationship:
1
Justification:
Different doses were tested, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor. The factor for duration will become updated with new studies in near future. See justification attached
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
1
Justification:
No toxicodynamic differences between species; see justification attached.
AF for intraspecies differences:
5
Justification:
ECHA default factor.
AF for the quality of the whole database:
1
Justification:
Results were based on key Klimisch 1-2 studies (and possible supporting studies).
AF for remaining uncertainties:
1
Justification:
For remaining uncertainties that would result from the above assessment factors.
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
56.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA factors in combination with recent scientific literature
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key oral OECD 422 toxicity study available; no repeated dose dermal toxicity study available.
AF for dose response relationship:
1
Justification:
Different doses were tested, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor. The factor for duration will become updated with new studies in near future. See justification attached.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
No toxicodynamic differences between species; see justification attached.
AF for intraspecies differences:
5
Justification:
ECHA default factor.
AF for the quality of the whole database:
1
Justification:
Results were based on key Klimisch 1-2 studies (and possible supporting studies).
AF for remaining uncertainties:
1
Justification:
For remaining uncertainties that would result from the above assessment factors.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

DNELs were based upon following source information:


- A key subacute OECD No. 422 study was conducted with the registered substance in Wistar rats (12/sex/group) by oral gavage at 0 (distilled water), 60, 150 and 450 mg/kg bw/day (Hargitai, 2022). Parameters measured during the study included twice a day mortality checking, daily routine and weekly detailed observation of clinical signs, weekly body weight and food consumption measurements and clinical pathology evaluation (including haematology, coagulation, clinical chemistry and urinalysis). Neurological assessment (Functional Observation Battery (FOB) including measurements of the landing foot splay, grip strength as well as locomotor activity measurement) was performed during the last week of the treatment for each sex. Reproductive performance is reported under Section 7.8. At termination (Day 28 for males, PPD (Post-partum Day) 14 for females), necropsy with macroscopic examination was performed. Weights of selected organs were recorded, and representative tissues/organs were sampled and preserved in appropriate fixatives from the adult animals or F1 animals. The thyroxine (T4) levels in the PND (Post-natal Day) 13 pups and parental males were also determined. For the adult animals, a detailed histological examination was performed on the selected list of retained organs of 5 animals/sex in the Control and High dose groups, the retained reproductive organs of all Control and High dose animals, stomach and thymus from all animals, the found dead animal or all organs with relevant macroscopic changes, and the male / female mating pair where no liveborn pups were achieved. Dosing formulations were analysed for concentration and/or homogeneity on three occasions during the study. Overall, the formulations were considered adequate for the study. In summary, under the conditions of this study the daily administration of TENSOMILD H026 (containing Disodium lauryl sulfosuccinate (EC 939-638-8) as active ingredient) by oral gavage to Wistar rats at dose levels of 60, 150 or 450 mg/kg bw/day (Low, Mid and High dose groups, respectively) did not result in test item related mortality or clinical signs. Test item related adverse effect was observed on body weight parameters and food consumption in High dose (450 mg/kg bw/day) males. At the functional observation battery (FOB) and locomotor activity measurement, there were no changes in animal behaviour, general physical condition or in the reactions to different type of stimuli in test item treated groups when compared to control. No test item-related adverse effects were seen in the clinical pathology parameters. Increased liver weights in High dose females (450 mg/kg bw/day) were not confirmed at histopathology, but adaptive hypertrophy of 11-14% as seen in this study is often not visible at histopathology; the organ weight difference was considered as non-adverse. Test item-related changes were observed in the non-glandular stomach in both sexes of the Mid and High dose groups (150 and 450 mg/kg bw/day, respectively) with a dose dependent trend in incidence and severity, indicating local irritation by the test item; males were more affected. The changes in the non-glandular stomach observed in this study were considered due to the irritant nature of the test item and is considered as a local effect rather than systemic toxicity of the test item.


Based on the existing results of this study, the following No-Observed-Adverse-Effect Levels (NOAELs) were considered: The NOAEL for systemic toxicity of the parental generation: 150 mg/kg bw/day (based on body weight and food consumption effects in males at 450 mg/kg bw/day). The NOAEL for local toxicity of the parental generation: 60 mg/kg bw/day (based on the local irritation in the stomach in both sexes in the 150 and 450 mg/kg bw/day dose groups).


- A 90-day study was not available for the registered substance, however read across data were available from read-across substance in the same subgroup, CAS No. 37294-49-8 (disodium C-isodecyl sulphonatosuccinate). This key study for subchronic toxicity was performed in rats with test item containing ca. 50% active ingredient (Tegeris and Underwood, 1975) at 0.25%, 1.00% and 4.00% in the diet (corresponding to mean calculated test article intake of 188, 750 and 3000 mg act.ingr./kg bw/day). At the highest dose levels, it caused a significant difference in body weight gain, most probably related to an effect by the compound during absorption from the gastro-intestinal tract. There was one mortality in the high dosed females. Haematology and serum analysis also indicated toxicity at the high dose, whereas at the medium dose, only some organ-to-body weight changes were observed (e.g. liver weight increases in both sexes). Other organ-to-body weight changes were also observed at the high dose group (e.g. slightly decreased gonad weights in males; decreased gonad weight in females); increased relative kidney weights were observed in all female dose groups. Chronic renal disease (mild) was observed in 1/20 males and 6/20 females of the high dose groups. The high dose was considered to be toxic, whereas the changes of the medium dose may be considered adaptive. Therefore 1% (750  mg/kg bw/day) may be considered as NOAELand 0.25% (174 mg/kg bw/day) as NOEL.


- Subchronic toxicity testing with read-across substance CAS No. 90268-36-3 is planned and will be updated later when results are available (currently waived in the dossier).


- For risk assessment, the lowest NOAEL of 150 mg/kg bw/day with registered substance tested in the OECD 422 study was selected as dose descriptor for calculation of long term systemic DNELS. This approach was considered conservative, as the NOAEL with read across substance in subchronic study with dietary administration was much higher. Further justification of assessment factors is explained in the DNEL justification document attached to the endpoint summary.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.57 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA factors in combination with recent scientific literature.
Overall assessment factor (AF):
60
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 174 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key oral OECD 422 toxicity study available; no repeated dose inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
Different doses were tested in the various studies, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor. The factor for duration will become updated with new studies in near future. See justification attached.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
1
Justification:
No toxicodynamic differences between species; see justification attached.
AF for intraspecies differences:
10
Justification:
ECHA default factor.
AF for the quality of the whole database:
1
Justification:
Results were based on key Klimisch 1-2 studies (and possible supporting studies).
AF for remaining uncertainties:
1
Justification:
For remaining uncertainties that would result from the above assessment factors.
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28.13 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA factors in combination with recent scientific literature
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key oral OECD 422 toxicity study available; no repeated dose inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
Different doses were tested, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor. The factor for duration will become updated with new studies in near future. See justification attached
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
No toxicodynamic differences between species; see justification attached.
AF for intraspecies differences:
10
Justification:
ECHA default factor.
AF for the quality of the whole database:
1
Justification:
Results were based on key Klimisch 1-2 studies (and possible supporting studies).
AF for remaining uncertainties:
1
Justification:
For remaining uncertainties that would result from the above assessment factors.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.63 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA factors in combination with recent scientific literature
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable
AF for dose response relationship:
1
Justification:
Different doses were tested, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor. The factor for duration will become updated with new studies in near future. See justification attached.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
No toxicodynamic differences between species; see justification attached.
AF for intraspecies differences:
10
Justification:
ECHA default factor.
AF for the quality of the whole database:
1
Justification:
Results were based on key Klimisch 1-2 studies (and possible supporting studies).
AF for remaining uncertainties:
1
Justification:
For remaining uncertainties that would result from the above assessment factors.
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:
medium hazard (no threshold derived)

Additional information - General Population

DNELs were based upon following source information:


- A key subacute OECD No. 422 study was conducted with the registered substance in Wistar rats (12/sex/group) by oral gavage at 0 (distilled water), 60, 150 and 450 mg/kg bw/day (Hargitai, 2022). Parameters measured during the study included twice a day mortality checking, daily routine and weekly detailed observation of clinical signs, weekly body weight and food consumption measurements and clinical pathology evaluation (including haematology, coagulation, clinical chemistry and urinalysis). Neurological assessment (Functional Observation Battery (FOB) including measurements of the landing foot splay, grip strength as well as locomotor activity measurement) was performed during the last week of the treatment for each sex. Reproductive performance is reported under Section 7.8. At termination (Day 28 for males, PPD (Post-partum Day) 14 for females), necropsy with macroscopic examination was performed. Weights of selected organs were recorded, and representative tissues/organs were sampled and preserved in appropriate fixatives from the adult animals or F1 animals. The thyroxine (T4) levels in the PND (Post-natal Day) 13 pups and parental males were also determined. For the adult animals, a detailed histological examination was performed on the selected list of retained organs of 5 animals/sex in the Control and High dose groups, the retained reproductive organs of all Control and High dose animals, stomach and thymus from all animals, the found dead animal or all organs with relevant macroscopic changes, and the male / female mating pair where no liveborn pups were achieved. Dosing formulations were analysed for concentration and/or homogeneity on three occasions during the study. Overall, the formulations were considered adequate for the study. In summary, under the conditions of this study the daily administration of TENSOMILD H026 (containing Disodium lauryl sulfosuccinate (EC 939-638-8) as active ingredient) by oral gavage to Wistar rats at dose levels of 60, 150 or 450 mg/kg bw/day (Low, Mid and High dose groups, respectively) did not result in test item related mortality or clinical signs. Test item related adverse effect was observed on body weight parameters and food consumption in High dose (450 mg/kg bw/day) males. At the functional observation battery (FOB) and locomotor activity measurement, there were no changes in animal behaviour, general physical condition or in the reactions to different type of stimuli in test item treated groups when compared to control. No test item-related adverse effects were seen in the clinical pathology parameters. Increased liver weights in High dose females (450 mg/kg bw/day) were not confirmed at histopathology, but adaptive hypertrophy of 11-14% as seen in this study is often not visible at histopathology; the organ weight difference was considered as non-adverse. Test item-related changes were observed in the non-glandular stomach in both sexes of the Mid and High dose groups (150 and 450 mg/kg bw/day, respectively) with a dose dependent trend in incidence and severity, indicating local irritation by the test item; males were more affected. The changes in the non-glandular stomach observed in this study were considered due to the irritant nature of the test item and is considered as a local effect rather than systemic toxicity of the test item.


Based on the existing results of this study, the following No-Observed-Adverse-Effect Levels (NOAELs) were considered: The NOAEL for systemic toxicity of the parental generation: 150 mg/kg bw/day (based on body weight and food consumption effects in males at 450 mg/kg bw/day). The NOAEL for local toxicity of the parental generation: 60 mg/kg bw/day (based on the local irritation in the stomach in both sexes in the 150 and 450 mg/kg bw/day dose groups).


- A 90-day study was not available for the registered substance, however read across data were available from read-across substance in the same subgroup, CAS No. 37294-49-8 (disodium C-isodecyl sulphonatosuccinate). This key study for subchronic toxicity was performed in rats with test item containing ca. 50% active ingredient (Tegeris and Underwood, 1975) at 0.25%, 1.00% and 4.00% in the diet (corresponding to mean calculated test article intake of 188, 750 and 3000 mg act.ingr./kg bw/day). At the highest dose levels, it caused a significant difference in body weight gain, most probably related to an effect by the compound during absorption from the gastro-intestinal tract. There was one mortality in the high dosed females. Haematology and serum analysis also indicated toxicity at the high dose, whereas at the medium dose, only some organ-to-body weight changes were observed (e.g. liver weight increases in both sexes). Other organ-to-body weight changes were also observed at the high dose group (e.g. slightly decreased gonad weights in males; decreased gonad weight in females); increased relative kidney weights were observed in all female dose groups. Chronic renal disease (mild) was observed in 1/20 males and 6/20 females of the high dose groups. The high dose was considered to be toxic, whereas the changes of the medium dose may be considered adaptive. Therefore 1% (750 mg/kg bw/day) may be considered as NOAEL and 0.25% (174 mg/kg bw/day) as NOEL.


- Subchronic toxicity testing with read-across substance CAS No. 90268-36-3 is  planned and will be updated later when results are available (currently waived in the dossier).


- For risk assessment, the lowest NOAEL of 150 mg/kg bw/day with registered substance tested in the OECD 422 study was selected as dose descriptor for calculation of long term systemic DNELS. This approach was considered conservative, as the NOAEL with read across substance in subchronic study with dietary administration was much higher. Further justification of assessment factors is explained in the DNEL justification document attached to the endpoint summary.