Registration Dossier

Administrative data

Workers - 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

Workers - 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:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
AF for dose response relationship:
1
Justification:
as outlined in ECHA guidance document R8
AF for differences in duration of exposure:
2
Justification:
Extrapolation of exposure duration: sub-chronic to chronic (as outlined in ECHA guidance document R8).
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbit to human (as outlined in ECHA guidance document R8).
AF for other interspecies differences:
2.5
Justification:
Rabbit to Human (as outlined in ECHA guidance document R8).
AF for intraspecies differences:
5
Justification:
Workers (as outlined in ECHA guidance document R8).
AF for the quality of the whole database:
1
Justification:
as outlined in ECHA guidance document R8
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The physico-chemical properties of the substance and its use demonstrate that there is negligible potential for inhalation exposure to the substance; consequently, no inhalation DNELs have been derived.

ECHA Guidance Document Chapter R.8, Appendix R.8-8 on Acute Toxicity states that a DNEL for acute toxicity is only necessary if "an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures". No acute toxicity hazard has been identified for the substance and, thus, no acute classification is proposed. Consequently, in accordance with the ECHA guidance, acute DN(M)ELs for systemic effects are not required.

The long term DNEL for systemic effects via the dermal route has been derived through read-across to a 90 day repeat dose dermal study on 2-phenoxyethanol. The data presented for material 2-phenoxyethanol (EC 204-589-7) is considered appropriate for read-across to EC 202-228-8 and to aid in the generation of DNELs and concluding on classification. The justification for the use of this read across is located within IUCLID section 13.

A NOAEL of 500 mg/kg/day (top dose tested) was observed based on lack of significant toxicological effects observed in the study. The DNEL was determined to be 8.33 mg/kg bw/day, conservatively assuming 100% absorption in both species using an assessment factor of 60.

The 90 day repeat dose dermal study is selected as the key effect level, this is the study more closely reflects the potential intermittent exposure during manufacture and use by restricting treatment to 6 hr/day, 5 days/week and changing occlusive wraps daily.

This study is chosen in preference to the dermal developmental toxicity/teratogenicity study (IUCLID section 7.8.2) in which significant maternal toxicity was observed at 600 mg/kg bw/day and the NOAEL was 300 mg/kg bw/day. The teratogenicity study involved 24 hour occlusive dermal exposure, the continuous exposure site occlusion method used may have contributed to alterations in the integrity of the epidermis as indicated by skin lesions in affected animals, resulting in enhanced absorption of the test material and subsequent development of hemolytic anemia.

Therefore the 90 day repeat dose study is considered more representative of potential exposure and is the more appropriate NOAEL to select as the key effect level.

The data available indicate the substance is not a dermal irritant or dermal sensitiser. Consequently, neither a short term or long-term DN(M)EL for local dermal effects is unnecessary.

EC-202-228-8 is classified as a Category 2 eye irritant based on the experimental data available. The in vitro eyeirritation study found EC 202-228-8 to be an eye irritant, it was therefore concluded in the interest of animal welfare it would be unethical to proceed to an in vivo eye irritation study. Therefore the eye irritation classification was determined using a weight of evidence approach. It is considered that the Testing And Evaluation Strategy in OECD TG 405 supports the view that there is no evidence that would require EC 202-228-8 to be classified as CLP Cat 1 (irreversible effects on the eye). It is considered that EC 202-228-8 does not to have potential to cause corrosion or serious eye damage because the in vitro skin test showed it to be non-irritating and the in vivo acute dermal toxicity test revealed no toxicity and no dermal effects after a 24 h application of the limit dose (2,000 mg/kg).  Although not yet validated, it is considered that the finding from the in vitro ocular test is good evidence that EC 202-228-8 is an eye irritant, and as such should be classified as a Cat 2 for eye irritant in accordance with CLP. As the registration substance is only classified as irritating to the eyes (H319), it was assigned as a 'Low Hazard', this complies with ECHA document "Guidance on information requirements and chemical safety assessment,Part E: Risk Characterisation, section E 3.4.2."

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:
4.167 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):
120
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
AF for dose response relationship:
1
Justification:
as outlined in ECHA guidance document R8
AF for differences in duration of exposure:
2
Justification:
Extrapolation of exposure duration: sub chronic to chronic (as outlined in ECHA guidance document R8).
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbit to human (as outlined in ECHA guidance document R8).
AF for other interspecies differences:
2.5
Justification:
Rabbit to Human (as outlined in ECHA guidance document R8).
AF for intraspecies differences:
10
Justification:
General Population (as outlined in ECHA guidance document R8).
AF for the quality of the whole database:
1
Justification:
as outlined in ECHA guidance document R8
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:
DNEL (Derived No Effect Level)
Value:
0.083 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
as outlined in ECHA guidance document R8
AF for differences in duration of exposure:
6
Justification:
Extrapolation of exposure duration: sub acute to chronic (as outlined in ECHA guidance document R8).
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human (as outlined in ECHA guidance document R8).
AF for other interspecies differences:
2.5
Justification:
Rat to Human (as outlined in ECHA guidance document R8).
AF for intraspecies differences:
10
Justification:
General Population (as outlined in ECHA guidance document R8).
AF for the quality of the whole database:
1
Justification:
as outlined in ECHA guidance document R8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The physico-chemical properties of the substance and its use demonstrate that there is negligible potential for inhalation exposure to the substance; consequently, no inhalation DNELs have been derived.

ECHA Guidance Document Chapter R.8, Appendix R.8-8 on Acute Toxicity states that a DNEL for acute toxicity is only necessary if "an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures". No acute toxicity hazard has been identified for the substance and, thus, no acute classification is proposed. Consequently, in accordance with the ECHA guidance, acute DN(M)ELs for systemic effects are not required.

The long term DNEL for systemic effects via the dermal route has been derived using a 90 day repeat dose dermal study on 2-phenoxyethanol. The data presented for material 2-phenoxyethanol (EC 204-589-7) is considered appropriate for read-across to EC 202-228-8 and to aid in the generation of DNELs and concluding on classification. The justification for the use of this read across is located within IUCLID section 13.

A NOAEL of 500 mg/kg/day (top dose tested) was observed based on lack of significant toxicological effects observed in the study. The DNEL was determined to be 4.167 mg/kg bw/day, conservatively assuming 100% absorption in both species using an assessment factor of 120.

The 90 day repeat dose dermal study is selected as the key effect level, this is based on the attempts to more closely reflect the potential intermittent exposure during manufacture and use by restricting treatment to 6 hr/day, 5 days/week and changing occlusive wraps daily. This study is chosen in preference to the dermal developmental toxicity/teratogenicity study (IUCLID section 7.8.2) in which significant maternal toxicity was observed at 600 mg/kg bw/day and the NOAEL was 300 mg/kg bw/day. The teratogenicity study involved 24 hour occlusive dermal exposure, the continuous exposure site occlusion method used may have contributed to alterations in the integrity of the epidermis as indicated by skin lesions in affected animals, resulting in enhanced absorption of the test material and subsequent development of hemolytic anemia. Therefore the 90 day repeat dose study is considered more representative of potential exposure and is the more appropriate NOAEL to select as the key effect level.

The long term DNELs for systemic exposure via the oral route have been derived using a 28 day repeat dose study which gave a NOAEL of 50 mg/kg/day based on changes in serum chemistry (details located in IUCLID section 7.5.1). The DNEL was determined to be 0.083 mg/kg bw/day, conservatively assuming 100% absorption in both species using an assessment factor of 600.

The data available indicate the substance is not a dermal irritant or dermal sensitiser. Consequently, neither a short term or long-term DN(M)EL for local dermal effects is unnecessary.

EC-202-228-8 is classified as a Category 2 eye irritant based on the experimental data available. The In Vitro eye irritation study found EC 202-228-8 to be an eye irritant, it was therefore concluded in the interest of animal welfare it would be unethical to proceed to an In Vivo eye irritation study. Therefore the eye irritation classification was determined using a weight of evidence approach. It is considered that the Testing And Evaluation Strategy in OECD TG 405 supports the view that there is no evidence that would require EC 202-228-8 to be classified as CLP Cat 1 (irreversible effects on the eye). It is considered that EC 202-228-8 does not to have potential to cause corrosion or serious eye damage because the in vitro skin test showed it to be non-irritating and the in vivo acute dermal toxicity test revealed no toxicity and no dermal effects after a 24 h application at the limit dose (2,000 mg/kg).  Although not yet validated, it is considered that the finding from the in vitro ocular test is good evidence that EC 202-228-8 is an eye irritant, and as such should be classified as a Cat 2 for eye irritant in accordance with CLP. As the registration substance is only classified as irritating to the eyes (H319), it was assigned as a 'Low Hazard', this complies with ECHA document"Guidance on information requirements and chemical safety assessment,Part E: Risk Characterisation, section E 3.4.2."