Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
534 mg/kg bw/day
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Additional information - workers

Acute/short-term local effects/ Long-term exposure local effects:

The skin sensitization potential of MBS was evaluated in guinea pigs and in studies with human volunteers. Skin sensitization was noted in guinea pigs after treatment with MBS (Wang 1988). Moreover, a clear allergic response (24/49) was noted in a Repeated Insult Patch test with human volunteers (Monsanto Co. 1982). This finding was confirmed by further Repeated Insult Patch tests with human volunteers (Monsanto Co 1986abc). Thus, based on the findings of the guinea pig test and the human Repeated Insult Patch-test studies, the test substance MBS is considered to be a skin sensitizer in humans. In consequence, an existing classification with R43 (24 ATP)/ skin sensitizer cat. 1 (regulation no. 1272/2008 GHS) is confirmed.

Based on the findings of the Repeated Insult Patch Test data with human volunteers and the data from the guinea pig assay a moderate skin sensitizing potential of MBS is suggested according to the categorization criteria published in REACH guidance document chapter R. 8.

The test substance showed skin irritating effects in guinea pigs (Wang 1988) and in a Repeated Insult Patch Test with human volunteers (Monsanto 1982). In addition the test substance was classified as eye irritating in New Zealand albino rabbits (Monsanto Co 1973). In consequence, an existing classification with R36/38 (24 ATP)/ eye irritating cat. 2, skin irritating cat. 2 (regulation no. 1272/2008 GHS) is confirmed. According to ECHA Guidance Document Part E: Risk Characterization, substances with R-phrases R36/38 (irritating to eyes and skin) are allocated to the moderate hazard category (dermal exposure).

In the limited inhalation study (Monsanto Co. 1981) exposed rats exhibited occasional nasal irritation which appeared to be concentration related (no more data). This finding was observed immediately after the 6 hour exposure period and disappeared by the next morning. Since the animals recovered from this lesion within 24 hours and this finding could not be correlated to histopathologic effects observed, the observation of nasal irritation in few MBS-exposed animals was not considered to be toxicologically adverse. No relevant local effects on the respiratory tract were observed up to 10.2 mg/m3. Thus, the DNEL inhalation (long-term exposure systemic: 7 mg/m3) covers the highest dose tested in this limited study.

Acute/short-term exposure systemic effects:

The acute systemic toxicity of the test substance MBS is very low after oral and dermal administration; LD50 values of >5000 mg/kg bw were obtained. Due to the very low oral and dermal acute toxicity of MBS it is proposed to limit exposure peaks to a factor of 8. This approach is generally in line with the regulatory procedure in Germany (see Technical Rule for Hazardous Substances 900 and according to REACH guidance document chapter 8, page 110)

DNEL short-term systemic dermal: 66.7 mg/kg bw/day x 8 = 533.6 mg/kg bw/day

To consider possible effects of nasal irritation it was concluded that the DNEL inhalation (long-term exposure systemic: 7 mg/m3) covers the DNEL acute/short-term systemic effects.

DNEL long-term exposure systemic:

Worker DNEL long-term systemic for oral route

The NOAEL of 50 mg/kg bw and day is taken for the risk assessment which based on the findings from the chronic feeding study (Monsanto Co 1981).

Startpoint: NOAEL 50 mg/kg bw and day

Differences in absorption Abs (oral-rat) / Abs (oral-human): 1

=> Corrected NOAEL 50 mg/kg bw/day

Interspecies differences: Allometric scaling: 4

Remaining interspecies differences: 2.5

Intraspecies differences: 5

Differences in duration of exposure (chronic to chronic): 1

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 50

=>Worker DNEL long-term for oral route-systemic: 1 mg/kg bw/day

Worker DNEL long-term sytemic for dermal route

The NOAEL of 2000 mg/kg bw and day is taken for the risk assessment which based on the findings from the 21-day dermal toxicity study (Monsanto Co 1981).

Startpoint: 2000 mg/kg bw and day

Differences in absorption Abs (dermal-rabbit) / Abs (dermal-human): 1

=> Corrected NOAEL 2000 mg/kg bw/day

Interspecies differences: Allometric scaling: 2.4

Remaining interspecies differences: 2.5

Intraspecies differences: 5

Differences in duration of exposure (subacute to chronic): 1*

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 30

=>Worker DNEL long-term for dermal route-systemic: 66.7 mg/kg bw/day

*No specific systemic effects noted for the dermal route, thus purpose of the assessment factor from the oral route.

Worker DNEL long-term systemic for inhalation route

The NOAEL of 50 mg/kg bw and day is taken for the risk assessment which based on the findings from the chronic feeding study (Monsanto Co 1981).

Startpoint: NOAEL 50 mg/kg bw and day

Respiratory volume rat (sRV) (worker (8 h): 1/0.38): 2.632

Differences in respiratory volume (default factor "light activity worker"): 0.67

Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 1*

=> Corrected NOAEC 88 mg/m3

Interspecies differences: Allometric scaling: 1

Remaining interspecies differences: 2.5

Intraspecies differences: 5

Differences in duration of exposure (chronic to chronic): 1

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 12.5

=>Worker DNEL long-term for inhalation route-systemic: 7 mg/m3

* Limited inhalation study available (Monsanto 1981)

DNEL fertility:

There is no reproductive toxicity screening test or generation study available. However, the data from the chronic toxicity study with MBS (Monsanto Co. 1982) are used for risk assessment (for more details see chapter toxicity to reproduction). Based on the findings from this study no adverse effects on reproduction organs were observed up to the highest dose tested; consequently no effects on fertility are assessed. Thus it was concluded that the DNEL long-term exposure systemic covers the fertility toxicity.

DNEL developmental toxicity:

The developmental toxicity of the test substance MBS was evaluated in a teratology study with Sprague-Dawley rats (Monsanto Co. 1981). Based on the findings of this study a NOAEL maternal of 100 mg/kg bw and day and a NOAEL developmental toxicity of 1000 mg/kg bw and day are suggested. Both NOAELs are clearly above the NOAEL systemic (50 mg/kg bw/and day) and thus it was concluded that the DNEL long-term exposure systemic covered the DNEL developmental toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.7 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/m³
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
266 mg/kg bw/day
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Acute/short-term local effects/ Long-term exposure local effects:

The skin sensitization potential of MBS was evaluated in guinea pigs and in studies with human volunteers. Skin sensitization was noted in guinea pigs after treatment with MBS (Wang 1988). Moreover, a clear allergic response (24/49) was noted in a Repeated Insult Patch test with human volunteers (Monsanto Co. 1982). This finding was confirmed by further Repeated Insult Patch tests with human volunteers (Monsanto Co 1986abc). Thus, based on the findings of the guinea pig test and the human Repeated Insult Patch-test studies, the test substance MBS is considered to be a skin sensitizer in humans. In consequence, an existing classification with R43 (24 ATP)/ skin sensitizer cat. 1 (regulation no. 1272/2008 GHS) is confirmed.

Based on the findings of the Repeated Insult Patch Test data with human volunteers and the data from the guinea pig assay a moderate skin sensitizing potential of MBS is suggested according to the categorization criteria published in REACH guidance document chapter R. 8.

The test substance showed skin irritating effects in guinea pigs (Wang 1988) and in a Repeated Insult Patch Test with human volunteers (Monsanto 1982). In addition the test substance was classified as eye irritating in New Zealand albino rabbits (Monsanto Co 1973). In consequence, an existing classification with R36/38 (24 ATP)/ eye irritating cat. 2, skin irritating cat. 2 (regulation no. 1272/2008 GHS) is confirmed. According to ECHA Guidance Document Part E: Risk Characterization, substances with R-phrases R36/38 (irritating to eyes and skin) are allocated to the moderate hazard category (dermal exposure).

In the limited inhalation study (Monsanto Co. 1981) exposed rats exhibited occasional nasal irritation which appeared to be concentration related (no more data). This finding was observed immediately after the 6 hour exposure period and disappeared by the next morning. Since the animals recovered from this lesion within 24 hours and this finding could not be correlated to histopathologic effects observed, the observation of nasal irritation in few MBS-exposed animals was not considered to be toxicologically adverse. No relevant local effects on the respiratory tract were observed up to 10.2 mg/m3. Thus, the DNEL inhalation (long-term exposure systemic: 1.7 mg/m3) covers the highest dose tested in this limited study.

Acute/short-term exposure systemic effects:

The acute systemic toxicity of the test substance MBS is very low after oral and dermal administration; LD50 values of >5000 mg/kg bw were obtained. Due to the very low oral and dermal acute toxicity of MBS it is proposed to limit exposure peaks to a factor of 8. This approach is generally in line with the regulatory procedure in Germany (see Technical Rule for Hazardous Substances 900 and according to recommendations given in the REACH guidance document chapter 8, page 110).

DNELshort-term systemic oral: 0.5 mg/kg bw/day x 8 = 4 mg/kg bw/day

DNEL short-term systemic dermal: 33.3 mg/kg bw/day x 8 = 266.4 mg/kg bw/day

To cover possible effects of nasal irritation it was concluded that the DNEL inhalation (long-term exposure systemic: 1.7 mg/m3) covers the DNEL acute/short-term systemic effects.

DNEL long-term exposure systemic:

General Public DNEL long-term systemic for oral route

The NOAEL of 50 mg/kg bw and day is taken for the risk assessment which based on the findings from the chronic feeding study (Monsanto Co 1981).

Startpoint: NOAEL 50 mg/kg bw and day

Differences in absorption Abs (oral-rat) / Abs (oral-human): 1

=> Corrected NOAEL 50 mg/kg bw/day

Interspecies differences: Allometric scaling: 4

Remaining interspecies differences: 2.5

Intraspecies differences: 10

Differences in duration of exposure (chronic to chronic): 1

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 100

=>General Public DNEL long-term for oral route-systemic: 0.5 mg/kg bw/day

General Public long-term sytemic for dermal route

The NOAEL of 2000 mg/kg bw and day is taken for the risk assessment which based on the findings from the 21-day dermal toxicity study (Monsanto Co 1981).

Startpoint: 2000 mg/kg bw and day

Differences in absorption Abs (dermal-rabbit) / Abs (dermal-human): 1

=> Corrected NOAEL 2000 mg/kg bw/day

Interspecies differences: Allometric scaling: 2.4

Remaining interspecies differences: 2.5

Intraspecies differences: 10

Differences in duration of exposure (subacute to chronic): 1*

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 60

=>General Public DNEL long-term for dermal route-systemic: 33.3 mg/kg bw/day

*No specific systemic effects noted for the dermal route, thus purpose of the assessment factor from the oral route.

General Public DNEL long-term systemic for inhalation route

The NOAEL of 50 mg/kg bw and day is taken for the risk assessment which based on the findings from the chronic feeding study (Monsanto Co 1981).

Startpoint: NOAEL 50 mg/kg bw and day

Respiratory volume rat (sRV) general public 1/1.15: 0.87

Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 1*

=> Corrected NOAEC: 44 mg/m3

Interspecies differences: Allometric scaling: 1

Remaining interspecies differences: 2.5

Intraspecies differences: 10

Differences in duration of exposure (chronic to chronic): 1

Dose response and endpoint specific/severity issues: 1

Quality of database: 1

Overall factor (product of individual factors): 25

=>General public DNEL long-term for inhalation route-systemic: 1.7 mg/m3

DNEL fertility:

There is no reproductive toxicity screening test or generation study available. However, the data from the chronic toxicity study with MBS (Monsanto Co. 1982) are used for risk assessment (for more details see chapter toxicity to reproduction). Based on the findings from this study no adverse effects on reproduction organs were observed up to the highest dose tested; consequently no effects on fertility are assessed. Thus it was concluded that the DNEL long-term exposure systemic covers the fertility toxicity.

DNEL developmental toxicity:

The developmental toxicity of the test substance MBS was evaluated in a teratology study with Sprague-Dawley rats (Monsanto Co. 1981). Based on the findings of this study a NOAEL maternal of 100 mg/kg bw and day and a NOAEL developmental toxicity of 1000 mg/kg bw and day are suggested. Both NOAELs are clearly above the NOAEL systemic (50 mg/kg bw/and day) and thus it was concluded that the DNEL long-term exposure systemic covered the DNEL developmental toxicity.

* Limited inhalation study available (Monsanto 1981)