2-Butyne-1,4-diol, polymer with methyloxirane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.82 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other:

Overall assessment factor (AF):

42.5

Modified dose descriptor starting point:

NOAEC

Value:

119.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

according to ECHA guideance  

AF for dose response relationship:

1

Justification:

already considered in point of departure correction

AF for differences in duration of exposure:

3.4

Justification:

according to BATKE et al. see discussion

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in point of departure correction

AF for other interspecies differences:

1

Justification:

see discussion

AF for intraspecies differences:

5

Justification:

rat -> worker according to ECHA R8 guideance

AF for the quality of the whole database:

1

Justification:

see discussion

AF for remaining uncertainties:

2.5

Justification:

according to ECHA R8 guideance

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:

0.8 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

170

Modified dose descriptor starting point:

NOAEL

Value:

136.8 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see discussion

AF for dose response relationship:

1

Justification:

already considered in point of departure correction

AF for differences in duration of exposure:

3.4

Justification:

according to BATKE et al. see discussion

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in point of departure correction

AF for other interspecies differences:

4

Justification:

see discussion

AF for intraspecies differences:

5

Justification:

rat -> worker according to ECHA R8 guideance

AF for the quality of the whole database:

1

Justification:

see discussion

AF for remaining uncertainties:

2.5

Justification:

according to ECHA R8 guideance

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

DNEL derivation for 2-Butyne-1,4-diol, comp. with methyloxirane CAS 61596-96-1 according to ECHA and ECETOC guidance documents

 

Even if the substance is classified as a skin irritant based on one LLNA information of source substance 1, there is no DNEL for local irritation / sensitisation derived, because the result is based on a read across with possible irritating effect (at the highest concentrations, but residual effects may also happen at the lower concentration). As it is known that irritation is a confounder in skin irritation studies (especially LLNA) leading to false positive results and a LLNA with source substance 2 (without irritating effects) shows no skin sensitisation the transferability of the positive result maybe questionable. Nevertheless to adress any concern it was decided to lable the substance as possible skin sensitizing and to add a qualitative risk assessment (see csr chapter 9) but not to derive DNELs based on this result.

Based on a comparison of the different available studies the most reliable and relevant NOAEL for the derivations of a DNEL can be obtained from the following studies:

 

Most sensitive record for systemic effects is:

The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (TNO Triskelion, 2013) conducted with a close homolgue ( 2-propyn-1-ol with methyloxiran CAS 38172-91-7) was identified as the appropriate starting point for DNEL derivation.NOAEL, (f/m, systemic, oral, rats):125 mg/kg bw.

As the active ingredient was 54.7 % this value is used for the correction of the NOAEL for RA use. Therefore we used a calculated NOAEL of 68.4 mg/kg bw for risk assessement.

The point of departure was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f., as therethere is no adequate subacute/subchronic studies for dermal or inhalation available.

1      Worker:

1.1     Inhalation (worker)

1.1.1     Point of departure correction (inhalation, worker)

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volumes of rats versus humans. The resulting corrected starting point for inhalation DNEC derivation for workers is equal to 119.7 mg/m³. 100% absorption is assumed.        

Point of departure correction: NOAEL oral -> NOAEC human (8h worker)

 

NOAEC human (8h worker) = oral NOAEL rat/ sRV_rat(AS)*(bw human/wRV) = 68.4/4 x 70/10 = 119.7 mg / m3 / 24h  

1.1.2     Assessment factors (AF) (inhalation, worker)

For DNEC derivation, the following assessment factors (AF) were applied to the corrected starting point:

Parameter	AF (ECHA)	Justification
Interspecies (rat -> human)	1	Already considered in starting point correction
Interspecies (remaining differences)	2.5	Standard factor as outlined in REACh Guidance document R.8
Intraspecies (worker)	5	Standard factor as outlined in REACh Guidance document R.8
Exposure duration	3.4	Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
Route to route (oral- inhalation)	1	Already considered in starting point correction
Dose response issues	1	NOAEL ->NOAEL
Quality	1	Reliability 1, well documented GLP-study
SUM AF	42.5

1.1.3     Calculation of DNEC (inhalation, worker)

DNEC= corrected NOAEC/SUM (AF) = 2119.7/42.5 = 2.82 mg/m³

 

1.2     Dermal (worker)

1.2.1     Point of departure correction (dermal, worker)

The point of departure was modified to get the corrected starting point for DNEL derivation. As the acute data shows that acute dermal toxicity is considerably lower than acute oral toxicity it is assumed that dermal absorption is considerably lower than oral uptake. The NOAEL was therefore corrected by a factor of 2.The inclusion of factor 2 means that 50% (instead of 100%) absorption is assumed for dermal absorption, and 100% for oral, which resulted in a corrected starting point for DNEL derivation for worker of 136.8 mg/kg bw/day.

Point of departure correction: NOAEL oral,rat -> NOAEL dermal, human

 

NOAEL human (worker) = oral NOAEL rat * (ABS_oral,rat/ ABS_dermal,human)= 68.4 * (100%/50%) = 136.8 mg/kg 

1.2.2     Assessment factors (AF) (dermal, worker)

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

Parameter	AF (ECHA)	Justification
Interspecies (rat -> human)	4	Recommended for the rat in REACh Guidance document R.8 for allometric scaling
Interspecies (remaining differences)	2.5	Standard factor as outlined in REACh Guidance document R.8
Intraspecies (worker)	5	Standard factor as outlined in REACh Guidance document R.8
Exposure duration	3.4	Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
Route to route (oral- dermal)	1	Already considered in starting point correction
Dose response issues	1	NOAEL -> NOAEL
Quality	1	Reliability 1, well documented GLP-study
SUM AF	170

 

1.2.3     Calculation of DNEL (dermal, worker)

DNEL= corrected NOAEL/SUM (AF) = 136.8/170 = 0.8 mg/m³

 

1.3     Oral (worker)

 

A long-term, oral systemic DNEL for worker is not relevant.

 

2      Overview derived DNEL/C´s

 

DNEC (inhalation, worker)                2.8 mg/m³

DNEL (dermal, worker)                     0.8 mg/kg bw/d

DNEL (oral, worker)                          not relevant

3. References

- Batke M, Escher S, Hoffmann-Doerr S, Melber C, MessingerH, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.

 

 - Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247-S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.

 

- Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.

-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.

-ECHA (2008). REACh Guidance document R.8

-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.

-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. Technical Report No. 110, October 2010.

 

QUALITATIVE CSA - SKIN IRRITATION/SENSITISATION AND EYE DAMAGE

(acute/long term exposure – local effects)

 

Worker

The available data for this effect do not provide quantitative dose-response information; thus, no

short-term local DNELs have been derived for dermal exposure and no quantitative risk assessment

was performed. Exposure assessment and risk characterization are performed on a qualitative basis.

The purpose of a qualitative risk characterization is to assess "the likelihood that effects are avoided

when implementing the exposure scenario…" (REACH Annex 1, Section 6.5) when there is no basis

for setting a DNEL/DMEL.

Implementation of risk management measures (RMMs) and operational conditions (OCs) need to be

proportional to the degree of concern for the health hazard presented by the substance. Therefore the

substance is categorized by the hazard according to ECHA Guidance on information requirements and

chemical safety assessment, Part E; November 2012.

Skin Sens. Cat 1Bisconsidered amoderatehazardfurtherMay cause damage to organs CAT 2as well asToxic if swallowed CAT 3are alsomoderate hazardstherefore the substance is categorized to themoderate hazard group.

RMM should be appropriate for hazard class and operational condition.Therefore a code of behavior

is communicated via the Safety Data Sheet (SDS) containing precaution statements and response

phrases and general handling instructions.

 

The communicated hazard and the recommended general behavior and RMM are:

H317: May cause an allergic skin reaction., H301: Toxic if swallowed.,

H373: May cause damage to organs….

and

P260: Do not breathe dust/fume/gas/mist/vapours/spray.

P264: Wash ... thoroughly after handling.

P270: Do no eat, drink or smoke when using this product.

P301+P310: IF SWALLOWED: Immediately call a POISON CENTER/doctor/…

P272: Contaminated work clothing should not be allowed out of the workplace.

and

P280: Wear protective gloves/protective clothing/eye protection/face protection.

 

A general RMM measure used for all scenarios handling skin sensitizing substances is to use appropriate gloves. Furthermore the substance is, according to the read across, as worst case, assumed to be a weak skin sensitizer. That means that larger amounts must come in contact to skin and even normal RMM may reduce the risk for skin sensitization. Therefore a review of this information on RMM and behavior advice given with the product indicates that, if the user complies to the advice, the risk of exposure toskinfor worker can be considered as adequately controlled.

 

General population

There are no customer uses; therefore, no risk concerning skin sensitization is derived for the general population.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

85

Modified dose descriptor starting point:

NOAEC

Value:

59.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

see discussion

AF for dose response relationship:

1

Justification:

already considered in point of departure correction

AF for differences in duration of exposure:

3.4

Justification:

according to BATKE et al. see discussion

AF for interspecies differences (allometric scaling):

1

Justification:

already considered in point of departure correction

AF for other interspecies differences:

1

Justification:

see discussion

AF for intraspecies differences:

10

Justification:

rat -> general poplulation according to ECHA R8 guideance

AF for the quality of the whole database:

1

Justification:

see discussion

AF for remaining uncertainties:

2.5

Justification:

according to ECHA R8 guideance

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:

0.4 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

340

Modified dose descriptor starting point:

NOAEL

Value:

136.8 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see discussion

AF for dose response relationship:

1

Justification:

already considered in point of departure correction

AF for differences in duration of exposure:

3.4

Justification:

according to BATKE et al. see discussion

AF for interspecies differences (allometric scaling):

4

Justification:

already considered in point of departure correction

AF for other interspecies differences:

1

Justification:

see discussion

AF for intraspecies differences:

10

Justification:

rat -> general popluation according to ECHA R8 guideance

AF for the quality of the whole database:

1

Justification:

see discussion

AF for remaining uncertainties:

2.5

Justification:

according to ECHA R8 guideance

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

340

Modified dose descriptor starting point:

NOAEL

Value:

68.4 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see discussion

AF for dose response relationship:

1

Justification:

already considered in point of departure correction

AF for differences in duration of exposure:

3.4

Justification:

according to BATKE et al. see discussion

AF for interspecies differences (allometric scaling):

4

Justification:

already considered in point of departure correction

AF for other interspecies differences:

1

Justification:

see discussion

AF for intraspecies differences:

10

Justification:

rat -> general popluation according to ECHA R8 guideance

AF for the quality of the whole database:

1

Justification:

see discussion

AF for remaining uncertainties:

2.5

Justification:

according to ECHA R8 guideance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

DNEL derivation for2-Butyne-1,4-diol, comp. with methyloxiraneCAS61596-96-1according to ECHA and ECETOC guidance documents

Even if the substance is classified as a skin irritant based on one LLNA information of source substance 1, there is no DNEL for local irritation / sensitisation derived, because the result is based on a read across with possible irritating effect (at the highest concentrations, but residual effects may also happen at the lower concentration). As it is known that irritation is a confounder in skin irritation studies (especially LLNA) leading to false positive results and a LLNA with source substance 2 (without irritating effects) shows no skin sensitisation the transferability of the positive result maybe questionable. Nevertheless to adress any concern it was decided to lable the substance as possible skin sensitizing and to add a qualitative risk assessment (see csr chapter 9) but not to derive DNELs based on this result.

 

Based on a comparison of the different available studies the most reliable and relevant NOAEL for the derivations of a DNEL can be obtained from the following studies:

 

Most sensitive record for systemic effects is:

The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (TNO Triskelion, 2013)

conducted with a close homolgue (2-propyn-1-ol with methyloxiran CAS 38172-91-7)

was identified as the appropriate starting point for DNEL derivation.NOAEL, (f/m, systemic, oral, rats):125 mg/kg bw

As the active ingredient was 54.7 % this value is used for the correction of the NOAEL for RA use. Therefore we used a calculated NOAEL of 68.4 mg/kg bw for risk assessement.

The point of departure was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f., as therethere is no adequate subacute/subchronic studies for dermal or inhalation available.

1      General population

1.1     Inhalation (general)

1.1.1     Point of departure correction (inhalation, general)

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volumes of rats versus humans. The resulting corrected starting point for inhalation DNEC derivation for the general population is 59.9 mg/m³.100% absorption is assumed.

 

Point of departure correction NOAEL oral -> NOAEC human (24h):

 

NOAEC human (24h general) = oral NOAEL rat/ sRV_rat(AS)*(bw human/wRV) = 68.4/4 x 70/20 = 59.9 mg / m3 / 24h

1.1.2     Assessment factors (AF) (inhalation, general)

For DNEC derivation, the following assessment factors (AF) were applied to the corrected starting point:

Parameter	AF (ECHA)	Justification
Interspecies (rat -> human)	1	Already considered in starting point correction
Interspecies (remaining differences)	2.5	Standard factor as outlined in REACh Guidance document R.8
Intraspecies (general)	10	Standard factor as outlined in REACh Guidance document R.8
Exposure duration	3.4	Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
Route to route (oral- inhalation)	1	Already considered in allometric scaling factor for starting point correction
Dose response issues	1	NOAEL -> NOAEL
Quality	1	Reliability 1, well documented GLP-study
SUM AF	85

 

1.1.3     Calculation of DNEC (inhalation, general)

DNEC= corrected NOAEC/SUM (AF) = 59.9/85 = 0.7 mg/m³

 

1.2     Dermal (general)

1.2.1     Point of departure correction (dermal, general)

The point of departure was modified to get the corrected starting point for DNEL derivation. As the acute data shows that acute dermal toxicity is considerably lower than acute oral toxicity it is assumed that dermal absorption is considerably lower than oral uptake. The NOAEL was therefore corrected by a factor of 2.The inclusion of factor 2 means that 50% (instead of 100%) absorption is assumed for dermal absorption, and 100% for oral, which resulted in a corrected starting point for DNEL derivation for worker of 250 mg/kg bw/day.

Point of departure correction: NOAEL oral,rat -> NOAEL dermal, human

 

NOAEL human (worker) = oral NOAEL rat * (ABS_oral,rat/ ABS_dermal,human) = 68.4 * (100%/50%) = 136.8 mg/kg 

1.2.2     Assessment factors (AF) (dermal, general)

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

Parameter	AF (ECHA)	Justification
Interspecies (rat -->human)	4	Recommended for the rat in REACh Guidance document R.8 for allometric scaling
Interspecies (remaining differences)	2.5	Standard factor as outlined in REACh Guidance document R.8
Intraspecies (worker)	10	Standard factor as outlined in REACh Guidance document R.8
Exposure duration	3.4	Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
Route to route (oral- dermal)	1	Already considered in starting point correction
Dose response issues	1	NOAEL --> NOAEL
Quality	1	Reliability 1, well documented GLP-study
SUM AF	340

 

1.2.3     Calculation of DNEL (dermal, general)

DNEL= corrected NOAEL/SUM (AF) = 136.8/340 = 0.40 mg/m³

 

1.3     Oral (general)

1.3.1    Point of departure correction (oral, general)

 

No modification for oral dose descriptor necessary as there is an adequate study available: NOAEL (oral, rat) -> NOAEL (oral, rat)

 

1.3.2     Assessment factors (AF) (oral, general)

 

The NOAEL of 68.4 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. Subsequently, the following assessment factors are taken into account for the final DNEL calculation for the oral route:

 

Parameter	AF (ECHA)	Justification
Interspecies (rat ->human)	4	Recommended for the rat in REACh Guidance document R.8 for allometric scaling
Interspecies (remaining differences)	2.5	Standard factor as outlined in REACh Guidance document R.8
Intraspecies (general)	10	Standard factor as outlined in REACh Guidance document R.8
Exposure duration	3.4	Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
Route to route (oral- oral)	1	Not necessary (oral-oral)
Dose response issues	1	NOAEL à NOAEL
Quality	1	Reliability 1, well documented GLP-study
SUM AF	340

 

1.3.3     Calculation of DNEL (oral, general)

DNEL=  NOAEL/SUM (AF) = 68.4/340 = 0.20 mg/m³

 

1.4     Oral short-term-systemic effects:

The long-term oral DNEL for systemic effects will also be sufficiently protective for short-term oral systemic effects. Therefore no DNEL was derived.

2      Overview derived DNEL/C´s

 

DNEC (inhalation, general)                0.7 mg/m³

DNEL (dermal, general)                    0.4 mg/kg bw/d

DNEL (oral, general)                          0.2 mg/kg bw/d

3. References

- Batke M, Escher S, Hoffmann-Doerr S, Melber C, MessingerH, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.

 

 - Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247-S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.

 

- Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.

-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.

-ECHA (2008). REACh Guidance document R.8

-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.

-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. Technical Report No. 110, October 2010.

QUALITATIVE CSA - SKIN IRRITATION/SENSITISATION AND EYE DAMAGE

(acute/long term exposure – local effects)

 

Worker

The available data for this effect do not provide quantitative dose-response information; thus, no

short-term local DNELs have been derived for dermal exposure and no quantitative risk assessment

was performed. Exposure assessment and risk characterization are performed on a qualitative basis.

The purpose of a qualitative risk characterization is to assess "the likelihood that effects are avoided

when implementing the exposure scenario…" (REACH Annex 1, Section 6.5) when there is no basis

for setting a DNEL/DMEL.

Implementation of risk management measures (RMMs) and operational conditions (OCs) need to be

proportional to the degree of concern for the health hazard presented by the substance. Therefore the

substance is categorized by the hazard according to ECHA Guidance on information requirements and

chemical safety assessment, Part E; November 2012.

Skin Sens. Cat 1Bisconsidered amoderatehazardfurtherMay cause damage to organs CAT 2as well asToxic if swallowed CAT 3are alsomoderate hazardstherefore the substance is categorized to themoderate hazard group.

RMM should be appropriate for hazard class and operational condition.Therefore a code of behavior

is communicated via the Safety Data Sheet (SDS) containing precaution statements and response

phrases and general handling instructions.

 

The communicated hazard and the recommended general behavior and RMM are:

H317: May cause an allergic skin reaction., H301: Toxic if swallowed.,

H373: May cause damage to organs….

and

P260: Do not breathe dust/fume/gas/mist/vapours/spray.

P264: Wash ... thoroughly after handling.

P270: Do no eat, drink or smoke when using this product.

P301+P310: IF SWALLOWED: Immediately call a POISON CENTER/doctor/…

P272: Contaminated work clothing should not be allowed out of the workplace.

and

P280: Wear protective gloves/protective clothing/eye protection/face protection.

 

A general RMM measure used for all scenarios handling skin sensitizing substances is to use appropriate gloves. Furthermore the substance is, according to the read across, as worst case, assumed to be a weak skin sensitizer. That means that larger amounts must come in contact to skin and even normal RMM may reduce the risk for skin sensitization. Therefore a review of this information on RMM and behavior advice given with the product indicates that, if the user complies to the advice, the risk of exposure toskinfor worker can be considered as adequately controlled.

 

General population

There are no customer uses; therefore, no risk concerning skin sensitization is derived for the general population.