Registration Dossier
Registration Dossier
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EC number: 295-714-4 | CAS number: 92128-22-8
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.1 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
- Value:
- 352.63 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose toxicity study available for the inhalation route.
- AF for dose response relationship:
- 1
- Justification:
- see "Discussion"
- AF for differences in duration of exposure:
- 2
- Justification:
- see "Discussion"
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- see "Discussion"
- AF for other interspecies differences:
- 2.5
- Justification:
- see "Discussion"
- AF for intraspecies differences:
- 5
- Justification:
- see "Discussion"
- AF for the quality of the whole database:
- 1
- Justification:
- see "Discussion"
- AF for remaining uncertainties:
- 1
- Justification:
- see "Discussion"
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.1 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
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 352.63 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose toxicity study available for the inhalation route.
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- see "Discussion"
- AF for differences in duration of exposure:
- 2
- Justification:
- see "Discussion"
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- see "Discussion"
- AF for other interspecies differences:
- 2.5
- Justification:
- see "Discussion"
- AF for intraspecies differences:
- 5
- Justification:
- see "Discussion"
- AF for the quality of the whole database:
- 1
- Justification:
- see "Discussion"
- AF for remaining uncertainties:
- 1
- Justification:
- see "Discussion"
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- DNEL extrapolated from long term DNEL
- Dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
1. SYSTEMIC EFFECTS - SHORT-TERM EXPOSURE (WORKERS)
a. DERMAL OR INHALATION ROUTE :
For the test substance no acute toxicity hazard leading to classification and labelling was identified. Acute toxicity studies in rats revealed LD50 values of > 4600 mg/kg bw (oral) or > 2000 mg/kg bw (dermal). Acute inhalation data are not available.
Furthermore, peak exposures via inhalation, dermal or oral route can be excluded according to the exposure scenarios for the test substance.
Therefore, the long-term DNELs derived from repeated dose toxicity covers the effects after acute exposure.
2. SYSTEMIC EFFECTS - LONG-TERM EXPOSURE (WORKERS)
Selection of the relevant starting point
Long-term exposure and fertility
There is no repeated dose toxicity study available for the dermal or inhalation route.
In a subacute (4-week) toxicity study in rats according to OECD TG 407 with oral (gavage) doses up to 800 mg/kg bw a NOAEL of 200 mg/kg bw was established for males and females (Eiben, 2010). In this study indications of liver toxicity were seen at 800 mg/kg bw (changes in liver function in males and adverse effects on the liver morphology in females). In a subchronic (13-week) toxicity study in rats according to OECD TG 408 with oral (gavage) doses up to 800/400 mg/kg bw the NOAEL was considered to be 400 mg/kg bw for males and 200 mg/kg bw for females (Wagenaar, 2020). In this study a combination of mortality, clinical signs, reduced food consumption, decreased body weights, macroscopic and histopathological findings were seen at 800/400 mg/kg bw. The histopathological findings in the caudal nasal cavity/nasopharynx (occasionally lung and trachea) were consistent with accidental aspiration of dose formulation, as a result of gastro-esophageal reflux after gavage dosing, and this was considered the cause of morbidity/mortality (for details see section 7.5.1).
In both studies necropsy and histopathology revealed no indication of adverse effects on organs of the male and female reproductive system after doses up to 800 mg/kg bw. Therefore, the NOAEL of 200 mg/kg bw also applies to the endpoint fertility.
Developmental toxicity
In a prenatal developmental toxicity study according to OECD TG 414 with oral (gavage) doses up to 1000 mg/kg bw a NOAEL of 100 mg/kg bw (maternal and developmental toxicity) was established for female rats (Müller, 2010). In this study no treatment-related malformations were observed up to and including 1000 mg/kg bw. Starting at 300 mg/kg bw skeletal findings indicating a retarded ossification occurred. These changes were seen at the 300 mg/kg level together with incidentally higher litter size which may have contributed to the marginally retarded ossification. A further sign of a retarded fetal development was a reduced fetal weight at the high dose level of 1000 mg/kg bw. In a further prenatal developmental toxicity study according to OECD TG 414 with oral (gavage) doses up to 300 mg/kg bw a NOAEL of 100 mg/kg bw (maternal and developmental toxicity) was established for female rabbits (van den Oetelaar, 2020). Severe maternal toxicity (clinical signs, reduced food consumption, mean body weight loss, reduced faeces production and mortality (sacrificed animals for animal welfare reasons)) was observed at 300 mg/kg bw. Moreover, insufficient litters were available for a thorough evaluation of developmental toxicity due to mortality in this dose group. Neither maternal nor developmental toxicity was seen in the 30 and 100 mg/kg bw groups.
Conclusion
In summary, the NOAEL of 200 mg/kg bw from the subchronic oral rat study will therefore be taken as the starting point for the DNEL calculation of systemic long-term effects. The lower NOAELs (100 mg/kg bw) of the two developmental toxicity studies in rats and rabbits do not argue against the use of 200 mg/kg bw as a starting point for the DNEL calculation, since the LOAELs (300 mg/kg bw) of these studies are lying above. Although the NOAELs of the prenatal developmental toxicity studies are lower by a factor of 2 than the NOAEL of the subchronic toxicity study, no separate DNEL needs to be calculated for the endpoint developmental toxicity, since the developmental studies cover the entire gestation period and therefore, in contrast to the long term exposure, there is no need for an additional time extrapolation factor (factor of 1 for developmental toxicity study vs. a factor of 2 for subchronic toxicity study).
a. ORAL OR DERMAL ROUTE :
NOAEL (rat) from the subchronic gavage study: 200 mg/kg bw / day
Penetration oral compared to dermal (both assumed 100 %): 1
AF for interspecies differences rat vs. human (allometric scaling): 4
AF for remaining interspecies differences: 2.5
AF for intraspecies differences in workers: 5
AF for extrapolation of exposure duration subchronic to chronic: 2
AF for reliability of dose-response: 1
AF for quality of whole database: 1
AF for remaining uncertainties: 1
Overall Assessment Factor: 100
Worker DNEL long-term for oral or dermal route - systemic: 2.0 mg/kg bw / day
b. INHALATION ROUTE :
NOAEL (rat) from the subchronic gavage study: 200 mg/kg bw / day
Correction of the starting point: 352.63 mg/m3
(200 mg/kg x 1/0.38 m3/kg x 6,7 m3/10 m3 x 1.0*)
AF for interspecies differences rat vs. human: 1 **
AF for remaining interspecies differences: 2.5
AF for intraspecies differences in workers: 5
AF for extrapolation of exposure duration subacute to chronic: 2
AF for reliability of dose-response: 1
AF for quality of whole database: 1
AF for remaining uncertainties: 1
Overall Assessment Factor: 25
Worker DNEL long-term for inhalation route - systemic: 14.1 mg/m3
* Correction of the starting point according to ECHA Guidance, Chapter R.8 (May 2008), Figure R.8-3
** No allometric scaling factor required according to ECHA Guidance, Chapter R.8 (May 2008), Table R.8-4 since already covered by correction of starting point
3. LOCAL EFFECTS - SHORT-TERM AND LONG-TERM EXPOSURE (WORKERS)
a. DERMAL ROUTE :
The substance is a skin sensitizer as well as corrosive to the skin. There are no studies available to clearly define a threshold for local toxicity after dermal application. Therefore, no DNEL for skin sensitization is calculated as the relationship between skin dose and response is not clear and there is no validated method of DNEL calculation for skin sensitization. According to the potency categorisation approach the test substance is classified as a moderate skin sensitizer based on a guinea pig maximization test (GPMT according OECD TG 406: 3 % induction conc., ≥ 90 % incidence of sensitization; Dreist and Kolb, 1993). Furthermore, the test substance proved to be corrosive to the skin of rabbits in a dermal irritation test according to OECD TG 404 (Suberg, 1984).
Regarding local effects the sensitization potential (Cat 1) as well as the corrosive potential (Cat 1C) needs to be considered in the selection of the respective risk management measures and operational conditions (RMMs/OCs) at the workplaces. Based on the local effects observed, the test substance is allocated to the moderate hazard band.
b. INHALATION ROUTE :
According to the ECHA guidance documents the DNEL calculation for compounds without fully valid long-term inhalation study is usually based on oral studies. This extrapolation covers the systemic effects of the compound. For non-irritating compounds it can be assumed that the potential local effects will be covered by the derived systemic DNEL. For compounds with irritating or corrosive properties the derived systemic DNEL might not cover potential local effects.
Data on inhalation toxicity of the substance are not available and therefore the threshold for local effects, in contrast to systemic toxicity, is not known. A toxicological working group within the German VCI* discussed the derivation of a DNEL for local irritating compounds with a limited database (without relevant inhalation toxicity data). The experts derived upper limit values for irritating and corrosive compounds based on available data. In particular, the working group evaluated the German MAK values published in the TRGS 900 in 2009. For irritating compounds labelled with R36 or R38 but without detectable irritation threshold from available data the experts derived a generic upper limit value of 10 mg/m3; for compounds with corrosive properties (R34 or R35) a respective value of 1 mg/m3 was derived.
Since the test substance was corrosive to the skin of rabbits in a dermal irritation test according to OECD TG 404 (Suberg, 1984) an upper limit value of 1 mg/m3 is proposed as a long-term inhalation DNEL for local effects, which is lower than the systemic long-term DNEL calculated as 14.1 mg/m3. This limit value also applies as a short-term inhalation DNEL for local effects.
* VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 352.63 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose toxicity study available for the inhalation route.
- AF for dose response relationship:
- 1
- Justification:
- see "Discussion"
- AF for differences in duration of exposure:
- 2
- Justification:
- see "Discussion"
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- see "Discussion"
- AF for other interspecies differences:
- 2.5
- Justification:
- see "Discussion"
- AF for intraspecies differences:
- 10
- Justification:
- see "Discussion"
- AF for the quality of the whole database:
- 1
- Justification:
- see "Discussion"
- AF for remaining uncertainties:
- 1
- Justification:
- see "Discussion"
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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):
- 50
- DNEL extrapolated from long term DNEL
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 352.63 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose toxicity study available for the inhalation route.
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- see "Discussion"
- AF for differences in duration of exposure:
- 2
- Justification:
- see "Discussion"
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- see "Discussion"
- AF for other interspecies differences:
- 2.5
- Justification:
- see "Discussion"
- AF for intraspecies differences:
- 10
- Justification:
- see "Discussion"
- AF for the quality of the whole database:
- 1
- Justification:
- see "Discussion"
- AF for remaining uncertainties:
- 1
- Justification:
- see "Discussion"
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- DNEL extrapolated from long term DNEL
- Dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
Exposure of the general population to the substance via the dermal route was not identified.
1. SYSTEMIC EFFECTS - SHORT-TERM EXPOSURE (GENERAL POPULATION) -
a. ORAL OR INHALATION ROUTE :
For the test substance no acute toxicity hazard leading to classification and labelling was identified. Acute toxicity studies in rats revealed LD50 values of > 4600 mg/kg bw (oral) or > 2000 mg/kg bw (dermal). Acute inhalation data are not available. Furthermore, peak exposures via inhalation, dermal or oral route can be excluded according to the exposure scenarios for the test substance.
Therefore, the long-term DNEL derived from repeated dose toxicity covers the effects after acute exposure.
2. SYSTEMIC EFFECTS - LONG-TERM EXPOSURE (GENERAL POPULATION)
Selection of the relevant starting point
Long-term exposure and fertility
There is no repeated dose toxicity study available for the dermal or inhalation route.
In a subacute (4-week) toxicity study in rats according to OECD TG 407 with oral (gavage) doses up to 800 mg/kg bw a NOAEL of 200 mg/kg bw was established for males and females (Eiben, 2010). In this study indications of liver toxicity were seen at 800 mg/kg bw (changes in liver function in males and adverse effects on the liver morphology in females). In a subchronic (13-week) toxicity study in rats according to OECD TG 408 with oral (gavage) doses up to 800/400 mg/kg bw the NOAEL was considered to be 400 mg/kg bw for males and 200 mg/kg bw for females (Wagenaar, 2020). In this study a combination of mortality, clinical signs, reduced food consumption, decreased body weights, macroscopic and histopathological findings were seen at 800/400 mg/kg bw. The histopathological findings in the caudal nasal cavity/nasopharynx (occasionally lung and trachea) were consistent with accidental aspiration of dose formulation, as a result of gastro-esophageal reflux after gavage dosing, and this was considered the cause of morbidity/mortality (for details see section 7.5.1).
In both studies necropsy and histopathology revealed no indication of adverse effects on organs of the male and female reproductive system after doses up to 800 mg/kg bw. Therefore, the NOAEL of 200 mg/kg bw also applies to the endpoint fertility.
Developmental toxicity
In a prenatal developmental toxicity study according to OECD TG 414 with oral (gavage) doses up to 1000 mg/kg bw a NOAEL of 100 mg/kg bw (maternal and developmental toxicity) was established for female rats (Müller, 2010). In this study no treatment-related malformations were observed up to and including 1000 mg/kg bw. Starting at 300 mg/kg bw skeletal findings indicating a retarded ossification occurred. These changes were seen at the 300 mg/kg level together with incidentally higher litter size which may have contributed to the marginally retarded ossification. A further sign of a retarded fetal development was a reduced fetal weight at the high dose level of 1000 mg/kg bw. In a further prenatal developmental toxicity study according to OECD TG 414 with oral (gavage) doses up to 300 mg/kg bw a NOAEL of 100 mg/kg bw (maternal and developmental toxicity) was established for female rabbits (van den Oetelaar, 2020). Severe maternal toxicity (clinical signs, reduced food consumption, mean body weight loss, reduced faeces production and mortality (sacrificed animals for animal welfare reasons)) was observed at 300 mg/kg bw. Moreover, insufficient litters were available for a thorough evaluation of developmental toxicity due to mortality in this dose group. Neither maternal nor developmental toxicity was seen in the 30 and 100 mg/kg bw groups.
Conclusion
In summary, the NOAEL of 200 mg/kg bw from the subchronic oral rat study will therefore be taken as the starting point for the DNEL calculation of systemic long-term effects. The lower NOAELs (100 mg/kg bw) of the two developmental toxicity studies in rats and rabbits do not argue against the use of 200 mg/kg bw as a starting point for the DNEL calculation, since the LOAELs (300 mg/kg bw) of these studies are lying above. Although the NOAELs of the prenatal developmental toxicity studies are lower by a factor of 2 than the NOAEL of the subchronic toxicity study, no separate DNEL needs to be calculated for the endpoint developmental toxicity, since the developmental studies cover the entire gestation period and therefore, in contrast to the long term exposure, there is no need for an additional time extrapolation factor (factor of 1 for developmental toxicity study vs. a factor of 2 for subchronic toxicity study).
a. ORAL ROUTE :
NOAEL (rat) from the subchronic gavage study: 200 mg/kg bw / day
Penetration oral compared to dermal (both assumed 100 %): 1
AF for interspecies differences rat vs. human (allometric scaling): 4
AF for remaining interspecies differences: 2.5
AF for intraspecies differences in general population: 10
AF for extrapolation of exposure duration subchronic to chronic: 2
AF for reliability of dose-response: 1
AF for quality of whole database: 1
AF for remaining uncertainties: 1
Overall Assessment Factor: 200
General population DNEL long-term for oral route - systemic: 1.0 mg/kg bw / day
b. INHALATION ROUTE :
NOAEL (rat) from the subchronic gavage study: 200 mg/kg bw / day
Correction of the starting point: 352.63 mg/m3
(200 mg/kg x 1/0.38 m3/kg x 6,7 m3/10 m3 x 1.0*)
AF for interspecies differences rat vs. human: 1 **
AF for remaining interspecies differences: 2.5
AF for intraspecies differences in general population: 10
AF for extrapolation of exposure duration subchronic to chronic: 2
AF for reliability of dose-response: 1
AF for quality of whole database: 1
AF for remaining uncertainties: 1
Overall Assessment Factor: 50
General population DNEL long-term for inhalation route - systemic: 7.1 mg/m3
* Correction of the starting point according to ECHA Guidance, Chapter R.8 (May 2008), Figure R.8-3
** No allometric scaling factor required according to ECHA Guidance, Chapter R.8 (May 2008), Table R.8-4 since already covered by correction of starting point
3. LOCAL EFFECTS - SHORT-TERM AND LONG-TERM EXPOSURE (GENERAL POPULATION) -
INHALATION ROUTE :
According to the ECHA guidance documents the DNEL calculation for compounds without fully valid long-term inhalation study is usually based on oral studies. This extrapolation covers the systemic effects of the compound. For non-irritating compounds it can be assumed that the potential local effects will be covered by the derived systemic DNEL. For compounds with irritating or corrosive properties the derived systemic DNEL might not cover potential local effects.
Data on inhalation toxicity of the substance are not available and therefore the threshold for local effects, in contrast to systemic toxicity, is not known.
A toxicological working group within the German VCI* discussed the derivation of a DNEL for local irritating compounds with a limited database (without relevant inhalation toxicity data). The experts derived upper limit values for irritating and corrosive compounds based on available data. In particular, the working group evaluated the German MAK values published in the TRGS 900 in 2009. For irritating compounds labelled with R36 or R38 but without detectable irritation threshold from available data the experts derived a generic upper limit value for workers of 10 mg/m3; for compounds with corrosive properties (R34 or R35) a respective worker value of 1 mg/m3 was derived.
Since the test substance was corrosive to the skin of rabbits in a dermal irritation test according to OECD TG 404 (Suberg, 1984) an upper limit value of 1 mg/m3 is proposed as a long-term inhalation DNEL for local effects in workers. This limit value also applies as a short-term inhalation DNEL for local effects. Since no expert-derived upper limit value for local effects is available for the general population, it is suggested to take the upper limit value of 1 mg/m3 as short-term and long-term inhalation DNEL for local effects in the general population as well. This limit value is lower than the systemic long-term DNEL of 7.1 mg/m3 calculated for the general population.
* VCI (Verband der chemischen Industrie e.V.): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Unpublished paper of VCI Arbeitskreis "Toxikologie", 21.01.2010
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