Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.41 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
52.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr=NOAELoral*(1/0.38 m³/kg/d)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 700 mg/kg/d*(1/0.38 m³/kg/d)*(0.5*1)*0.67=617 mg/m³. It is assumed that oral absorption rate is 50% of that of inhalation absorption. ABSoral/rat=oral absorption rate in rats, ABSinh./human=inhalation absorption rate in humans
AF for dose response relationship:
1
Justification:
a true NOAEL is available
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not necessary for inhalation route
AF for other interspecies differences:
2.5
Justification:
default value for remaining differences
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
good quality data available
AF for remaining uncertainties:
1
Justification:
the data provided covers the addressed tonnage band
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:
2.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
175
Modified dose descriptor starting point:
NOAEL
DNEL value:
360 mg/kg bw/day
AF for dose response relationship:
1
Justification:
a true NOAEL is available
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
7
Justification:
default value for mice
AF for other interspecies differences:
2.5
Justification:
default value for remaining differences
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
good quality data available
AF for remaining uncertainties:
1
Justification:
the provided data covers the addressed tonnage band
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:
0.004 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
other: LOEL (rat) = 11.25 mg/kg bw/day
AF for dose response relationship:
3
Justification:
EC3/NOAEL extrapolation
AF for differences in duration of exposure:
1
Justification:
no time-dependence expected for local skin effects
AF for interspecies differences (allometric scaling):
1
Justification:
not necessary for local effects
AF for other interspecies differences:
1
Justification:
not necessary for local effects
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
good quality data available
AF for remaining uncertainties:
1
Justification:
the data provided covers the tonnage band
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

Sodium thioglycolate (NaTG) was chosen for long-term animal studies to act as an appropriate surrogate for thioglycolic acid and its salts. Correcting the NOAEL for molecular weight is regarded as not necessary, as it has only minor effects on this value and finally on the DNELs.

Inhalation, systemic effects, long-term exposure

In a 90-day oral toxicity study performed in rats with NaTG, a NOAEL of 20 mg/kg bw/day for systemic toxicity has been determined.

Step 1) Relevant dose descriptor

NOAELRat= 20 mg/kg bw/day

Step 2) Modification of starting point

Conversion into inhalatory NOAEC (in mg/m³) by using an 8-hour standard respiratory volume for the rat

Correction for differences between oral and inhalation absorption

Correction for differences in 8-hour inhalative volumes between workers in rest and workers under light activity

 

 

0.38 m³ /kg bw

 

1

 

6.7 m³ / 10 m³

Step 3) Assessment factors

Interspecies

Intraspecies

Exposure duration

Dose response

Quality of database

 

2.5

5

2

1

1

DNEL Value

1.41 mg/m³

(20 x 1/0.38 x 1 x 6.7/10 x 1/(2.5 x 7 x 5 x 2 x 1 x 1))

 

Dermal, systemic effects

No difference between oral and inhalation absorption is assumed.

The available data suggests no relevant differences in dermal absorption among the salts of the thioglycolic acid.

In 90-day studies performed in rats and mice with NaTG, the dermal NOAELs for systemic toxicity were higher than 180 and 360 mg/kg bw/day, respectively. The NOAEL > 360 mg/kg bw/day determined in mice is selected as a relevant dose-descriptor.

Step 1) Relevant dose descriptor

NOAELMouse> 360 mg/kg bw/day

Step 2) Modification of starting point

Correction for substance differences in dermal absorption

 

1

Step 3) Assessment factors

Interspecies

Intraspecies

Exposure duration

Dose response

Quality of database

 

2.5 x 7

5

2

1

1

DNEL Value

> 2.06 mg/kg bw/day

(360 x 1/(2.5 x 7 x 5 x 2 x 1 x 1))

 

Dermal, local effects

In a 90-day dermal toxicity study perfomed in rats with NaTG, the LOEL for local effects at the site of application (skin irritation) was 11.25 mg/kg bw.

Step 1) Relevant dose descriptor

LOELRat= 11.25 mg/kg bw/day

Step 2) Modification of starting point

Modification to LOEL for dermal irritation (in mg/cm²/day)

 

0.25 kg / 44.5 cm²

Step 3) Assessment factors

Interspecies (local effects)

Intraspecies

Exposure duration

Dose response (LOEL/NAEL extrapolation)

Quality of database

 

1

5

1

3

1

DNEL Value

0.004 mg/cm²/day

(11.25 x 0.25/44.5 x 1/(1 x 5 x 1 x 3 x 1))

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for dose response relationship:
1
Justification:
no time-dependence expected for local skin irritation
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral 90 day study
AF for interspecies differences (allometric scaling):
4
Justification:
experimental animal was rat
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
good quality data available
AF for remaining uncertainties:
1
Justification:
the provided data covers the addressed tonnage band
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:
no hazard identified
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

DNELs for the general population have not been proposed because thioglycolates are generally used as an ingredient in cosmetic products. According to Article 14, paragraph 5(b) of Regulation No. (EC) 1907/2006 (REACh), the chemical safety report does not need to include considerations of the risk to human health from end uses in cosmetic products within the scope of Regulation (EC) No. 1223/2009 (Cosmetics Regulation).