Methanesulphonic acid

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.76 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

242 mg/m³

Explanation for the modification of the dose descriptor starting point:

not necessary: based on no systemic effects at the highest dose in sub acute inhalation study

AF for dose response relationship:

1

Justification:

already considered in route to route

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in route to route

AF for other interspecies differences:

1

AF for intraspecies differences:

3

Justification:

3 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: according to german official authority risk assessment

Overall assessment factor (AF):

36

Dose descriptor:

LOAEC

AF for dose response relationship:

2

Justification:

2 for LOAEL to NAEL translation due to dose response relation

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in route to route

AF for other interspecies differences:

1

AF for intraspecies differences:

3

Justification:

3 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

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:

19.44 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

1 400 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no necessary: based on no systemic effects at the highest dose in OECD 421 study

AF for dose response relationship:

1

Justification:

already considered in route to route

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

4

Justification:

AS rat according to ECHA guideance

AF for other interspecies differences:

1

AF for intraspecies differences:

3

Justification:

3 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

Acute/short term exposure

DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Relevant Toxicology Data:

Methane sulphonic acid (MSA)is moderately toxic by oral and dermal exposure. It was not mutagenic and did not induce chromosomal changes. In a repeated dose toxicity study by inhalation exposure, a transient reduction in mean body weight gain and some microscopic findings in the nasal turbinates were the only adverse findings. The LOAEL for local effects was 25 mg/m³ (nominal) and the NOAEL for systemic toxicity was 242 mg/m³(analytical). In a reproductive screening test, no effects for parental toxicity, reproductive performance and on progency were observed up to the highest dosage tested (1000 mg/kg/day). No birth abnormalities were observed in the offsprings of rats given a dosage of 400 mg/kg/day during days 6 through 15 of pregnancy.

 

Processing the DNEL

 

- Identification of the most relevant dose descriptor:

The 28-days inhalation toxicity study in rats with MSA was considered to be the appropriate study for DNEL derivation – inhalation effects (see DNEL / OEL derivation for local effects). Additionally,reproductive screening test (OECD 421) in ratswas considered to be the appropriate study for DNEL derivation – oral and dermal effects.In this study, rats were dosed orally with MSA for 42 days in males and at least 54 days in females, which is considered equivalent to sub-acute repeated dose study.

 

- Mode of action:

MSA is corrosive; No mutagenic potential is apparent with MSA.

 

Derivation of DNELs

 

- DNEL derivation – inhalation (official german OEL available)

The german national authority (BAuA) has shortly published an official german OEL (Arbeitsplatzgrenzwert). The AGW (Arbeitsplatzgrenzwert, transl. occupational exposure level (OEL)) was defined as

 

0,7 mg/m³

 

with an exceedance factor of 1.

The rational for this value was given as follows (see chapter 13, page 9): ”Methan sulfonic acid is a local effective substance. In a subacute inhalation toxicity study with rats no NOAEL could be determined. Already for the lowest tested concentration of 25mg/m³local effects in nasal cavity were observed (hyperplasia of goblet cells and degeneration of olfactory epithelia).  Hyperplasia of goblet cells is judged as adaptive and less critical than degeneration of olfactory epithelia.

Point of departure for AGW derivation is the LOAEL of 25 mg/m3. As in the sub acute inhalation toxicity study no NOAEL could be determined and extrapolation from LOAEL to NAEL using an extrapolation factor of 2 is performed. This extrapolation factor is considered as sufficient despite the low slope of the dose response curve of the olfactory ephithelia degeneration, as the effect is minimal marked. For time extrapolation (sub acute – chronic) the standard factor of 6 is used as no substance specific information concerning this extrapolation are available. As the critical toxicity is caused by the acidity based on the direct local cytotoxicity, an assessment factor of 3 is used for inter- and intra-species variability.

Take together AGW (OEL) of 0,7mg/m³for methan sulfonic acid is calculated based on a LOAEL of 25mg/m³”

Using the assessment factors of: 2 for LOAEL to NAEL translation, 6 for sub acute to chronic time extrapolation and 3 for inter- and intra-species variability. SUM AF = 36

LOAEL to NAEL translation as well as time extrapolation are in accordance with ECHA guidance factors, whereas inter / intra species variability is in accordance to ECETOC guidance.

 

- DNEL derivation – oral and dermal effects

As for oral and dermal effects no official values are available, the DNELs were derived using the following assumptions/assessmentfactors according to the same guideances used in the official german value.

- Selection of the dose descriptor:

Oral route /dermal systemic exposure:reproductive screening test in rats, NOAEL (systemic effects) = 1000 mg/kg bw.

- Modification of dose descriptor:

In order to adjust the NOAEL for the other/relevant exposures, a modification has to be made for workers.

 

Dermal/systemic exposure

Oral NOAEL	Absorption difference	Factor for study length	Corrected NOAEL
1000 mg/kg/day	1	7 days/5days	1400 mg/kg bw/d

 

-  Application of assessment factors:Assessment factors described in ECETOC (2003) Technical Report No. 86 and ECHA guideance:  

Assessment factor-accounting for Differences in		Default Value systemic effects	Default value local effects
Interspecies	Correction for differences in metabolic rate per body weight	4 *	-
	Remaining differences	1	1
Intraspecies	Worker (ECETOC)	3	3
Exposure duration	Subacute to chronic (ECHA)	6	6
Dose-response		1	1
Quality of whole database		1	1

* For oral/ dermal route

 

 

Inhalation route / systemic exposure 

 

Inhalation NOAEC	Factor for study length	Factor for standard respiratory volume man and 8-h exposure	Corrected NOAEC
242 mg/m3	6 h/8 h	6.7 m^3(8h) / 10 m^3(8h)	121.6 mg/ m^3

 

Corrected NOAEC	Sum of assessment factors applicable	DNELinhalative
121.6 mg/ m^3	3 x 6 = 18	6.76 mg/m^3

 

Dermal route/systemic exposure 

Corrected NOAEL	Sum of assessment factors applicable	DNELdermal
1400 mg/kg bw/day	4 x 3 x 6 =72	19.44 mg/kg bw

 

 

- Resulting DNELs 

Exposure pattern	DNEL
Acute inhalation – systemic effects	-
Acute dermal – local effects	-
Acute inhalation – local effects	-
Long-term dermal – systemic effects	19.44 mg/kg
Long-term inhalation – systemic effects	6.76 mg/m^3
Long-term oral – systemic effects	NA
Long-term dermal – local effects	-
Long-term inhalation – local effects	0.7 mg/m3

          NA: not applicable

 v

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.44 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEC

Value:

43.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

no necessary: based on no systemic effects at the highest dose in sub acute inhalation study

AF for dose response relationship:

1

Justification:

already considered in route to route

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in route to route

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

5 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.42 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

60

Dose descriptor:

LOAEC

AF for dose response relationship:

2

Justification:

2 for LOAEL to NAEL translation due to dose response relation (BAuA)

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in route to route

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

5 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

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:

8.33 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no necessary: based on no systemic effects at the highest dose in oral OECD 421 study

AF for dose response relationship:

1

Justification:

already considered in route to route

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

4

Justification:

AS rat according to ECHA guideance

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

5 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

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:

8.33 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: according to ECHA and ECETOC guideance (following offical BAUA approach)

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no necessary: based on no systemic effects at the highest dose in oral OECD 421 study

AF for dose response relationship:

1

Justification:

already considered no route to route transfer

AF for differences in duration of exposure:

6

Justification:

sub acute to chronic according to ECHA guideance

AF for interspecies differences (allometric scaling):

4

Justification:

AS rat according to ECHA guideance

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

5 for inter- and intra-species variability according to ECETOC / mechanism of action

AF for the quality of the whole database:

1

Justification:

quality ok, no RA, according to ECHA guideance

AF for remaining uncertainties:

1

Justification:

according to ECETOC (BAuA)

Acute/short term exposure

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Relevant Toxicology Data:Same as shown in workers

Processing the DNEL

- Identification and selection of dose descriptor: Same as shown in workers

- Modificationof dose descriptor:

In order to adjust the NOAEL for the other/relevant exposures, a modification has to be made for workers and the general public. 

Inhalation NOAEC	Factor for study length	Corrected NOAEC
242 mg/m3	6 h/24 h (5 days/7 days)	43.2 mg/ m^3

 

Inhalation/local exposure

Inhalation LOAEC	Factor for extrapolation from LOAEC to NOAEC	Corrected NOAEC
25 mg/m3	2 (same like in BAuA riskassessment)	12.5 mg/ m^3

 

 - Application of assessment factors:Assessment factors described in ECETOC (2003) Technical Report No. 86 and ECHA guideance were used. Ecetoc factors which are already used by the local german authority are used as they are based on mechanism of action.  

Assessment factor-accounting for Differences in		Default Value systemic effects	Default value local effects
Interspecies	Correction for differences in metabolic rate per body weight	4 *	-
	Remaining differences (ECETOC, BAuA)	1	1
Intraspecies	General population (ECETOC, BAuA)	5	5
Exposure duration	Subacute to chronic (ECHA)	6	6
Dose-response		1	1
Quality of whole database		1	1

* For oral/ dermal route

 

Oral Route / systemic exposure 

Corrected NOAEL	Sum of assessment factors applicable	DNELoral
1000 mg/kg bw/day	4 x 5 x 6 =120	8.33 mg/kg bw

           

   Inhalation route / systemic exposure 

Corrected NOAEC	Sum of assessment factors applicable	DNELinhalative
43.2 mg/ m^3	5 x 6 = 30	1.44 mg/m^3

           

   Inhalation route DNELs / local exposure 

Corrected NOAEC	Sum of assessment factors applicable	DNELinhalative
12.5 mg/m3	6 x 5 = 30	0.42 mg/m^3

 

Dermal route/systemic exposure 

Corrected NOAEL	Sum of assessment factors applicable	DNELdermal
1000 mg/kg bw/day	4 x 5 x 6 =120	8.33 mg/kg bw

 

 

Resulting DNELs 

Exposure pattern	DNEL
Acute inhalation – systemic effects	-
Acute dermal – local effects	-
Acute inhalation – local effects	-
Long-term dermal – systemic effects	8.33 mg/kg
Long-term inhalation – systemic effects	1.44 mg/m^3
Long-term oral – systemic effects	8.33 mg/kg
Long-term dermal – local effects	-
Long-term inhalation – local effects	0.42 mg/m3