Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 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
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”): assumption ABSoral-rat/ ABSderm-human =1
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
AF for differences in duration of exposure:
2
Justification:
see: TGD example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”)
AF for interspecies differences (allometric scaling):
4
Justification:
AF for Rat ; see example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”)
AF for other interspecies differences:
2.5
Justification:
see TGD ("remaining differences")
AF for intraspecies differences:
5
Justification:
see TGD (for worker AF = 5)
AF for the quality of the whole database:
1
Justification:
new GLP study; Klimisch 1
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 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):
50
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”): assumption ABSoral-rat/ ABSderm-human =1
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
AF for interspecies differences (allometric scaling):
4
Justification:
AF for Rat ; see example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”)
AF for other interspecies differences:
2.5
Justification:
see TGD ("remaining differences")
AF for intraspecies differences:
5
Justification:
see TGD (for worker AF = 5)
AF for the quality of the whole database:
1
Justification:
new GLP study; Klimisch 1
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

In acute oral and acute inhalation toxicity tests and in all other tests at present the substance showed no effects leading to classification and labelling. In particular the substance has no skin irritating, no skin sensitizing and no eye irritation properties that would lead to classification and labelling. According to "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health" APPENDIX R. 8-8 "...a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures". Based on present information the substance showed no effects leading to classification and labelling and hence the derivation of acute DNEL is not appropriate.

A 14 day inhalation study is available. No relevant effects were observed and the NOEC is greater than 1.03 mg/L which represents the highest concentration that was technically feasible in the study.

A 90 day oral repeated dose toxicity study was performed in rats according to OECD 408. Daily oral (gavage) administration of the test item to Wistar rats for 90 consecutive days at 100, 300 and 1000 mg/kg bw/day was associated with minor effects at the highest dose level only. High dose group findings included slight anaemia with lower RBC and HGB concentrations (females only), increased Albumin and consequently increased Total Protein concentrations, and increased A/G ratio in both sexes with association to statistically significant increased liver weight values (including the brain and body weight relative values) in females and statistically significant increased body weight relative values in males. Statistically significant increased kidney weight values (including the brain and body weight relative values) in females and statistically significant increased body weight relative values in males were observed after 90 days exposure without relevant histopathological changes. Although signs of reversibility were observed in recovery animals, the changes in female liver (brain weight relative value only), kidneys and haematology parameters persisted to some extent. No effects of toxicological relevance were observed at the low or mid dose levels.

In conclusion, the NOAEL of the test item administered by oral gavage to Wistar rats for 90 consecutive days is considered to be 300 mg/kg bw/day based on a precautionary worst case approach.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The substance trans-N1,N1,N4,N4-Tetrakis(2-hydroxyethyl)1,4-cyclohexanedicarboxamide is not used directly in consumer products. Hence, DNEL´s are not derived for general population.