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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.705 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:
17.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
96% bioavailability after oral administration (is already maximal)
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already applied in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.3 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
141 ng/m³
Explanation for the modification of the dose descriptor starting point:
Key acute oral toxicity study available; no acute inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
Various doses available; dose without effects considered as NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already applied in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties

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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.171 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:
17.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key oral repeated dose toxicity study contained all necessary toxicological parameters (in contrast to dermal repeated dose toxicity study).
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.012 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for local effects
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Sources and info for the DNEL calculations:

In a key oral acute toxicity study in female rats dosed at 80, 125, 160, 200 and 320 mg/kg bw, Chloroacetamide had an LD50 of 138 mg/kg bw (Hoechst, 1976). Deadly poisoned animals (125, 160, 200 and 320 mg/kg bw) showed impaired balance, gasping breathing and bended posture; no macroscopically effects were observed. 80 m/kg bw was considered as NOAEL.

In a key 90 day oral repeated dose study (Hoechst, 1985) 80 Wistar rats (40 males and 40 females) were administered at doses of 0, 20, 100 and 500 mg Chloroacetamide/kg feed /day (equivalent to 0, 2, 10 and 50 mg/kg bw/day). In the high dose group, reduced body weight gain/food consumption and increased leucocytes were observed, as well as decreased liver weights in females, and smaller testes, reduced testicular weights, proliferation of Leydig cells and depression - standstill of spermiogenesis in males. After a 29 -day recovery period, partial to complete regeneration was observed in the testis, therefore this was considered to be reversible. The NOAEL was 100 mg/kg feed, corresponding with 10 mg/kg bw/day.

In a 30 day dermal repeated dose toxicity (Hoechst, 1967) Chloroacetamide was tested without coverage in female rabbits at 25, 50, 100, 200 and 400 mg/kg bw /day (0.063, 0.13, 1.25, 0.50, 1.00 mL/kg bw/day). After the end of testing all surviving animals were observed for 3 days. In the 25 and 50 mg dose groups there were no findings. In the 100 mg dose group a slight body weight loss was observed during treatment and histological changes in liver, heart muscle and spleen. In the 200 mg dose group similar observations were done with a more significant weight loss. In the 400 mg dose group 3 animals died (1 on day 1, 2 and 3 respectively). Similar changes as in the 100 and 200 mg dose groups in liver, heart muscle and spleen were observed and a significant weight loss. In all dose groups there were local changes of the treated skin area (encrustation to induration). The dermal NOAEL was 50 mg/kg bw/day.

In a 13 weeks dermal toxicity repeated dose study, Konservierungsmittel CA 24 was applied to the shaved backs of male adult Wistar-rats, at doses of 12.5 and 50.0 mg/kg in Lanette (1 or 2%) or Aqua dest (2%). Neither test dependent or substance specific changes were observed in the growth parameters and histomorphological examinations. The dermal “no-effect” level of CA 24 in male adult rats is 50 mg/kg bw.Taking into account the 70% Chloroacetamide content and assuming that sodium benzoate was inactive on the skin, 35 mg act./kg bw was considered as local NOAEL. Based on the lower NOAEL, this was considered as key study. Considering a mean body weight of 300 g (based on study data) and a surface area of 325 cm2 (Derelanko, 2008; The Toxicologist's Pocket handbook p29), 10.5 mg was applied on 32.5 cm2 (10% body surface), corresponding to 0.32 mg/cm2. Compared to the rabbit NOAEL of 50 mg/kg bw and a mean body weight of 2.5 kg (based on study data) and a surface area of 1270 cm2 (Derelanko, 2008; The Toxicologist's Pocket handbook p29), 125 mg was applied on 127 cm2 (10% body surface), corresponding to 0.98 mg/cm2. Therefore the rat value was considered most conservative.

As the key 3-month dermal study (IBR, 1971; NOAEL = 50 mg/kg bw) did not have biochemistry and full histopathology, the NOAEL from the 90-day oral study was used as most conservative. In a key 90 day oral repeated dose study (Hoechst, 1985) 80 Wistar rats (40 males and 40 females) were administered at doses of 0, 20, 100 and 500 mg Chloroacetamide/kg feed /day (equivalent to 0, 2, 10 and 50 mg/kg bw/day). In the high dose group, reduced body weight gain/food consumption and increased leucocytes were observed, as well as decreased liver weights in females, and smaller testes, reduced testicular weights, proliferation of Leydig cells and depression - standstill of spermiogenesis in males. After a 29 -day recovery period, partial to complete regeneration was observed in the testis, therefore this was considered to be reversible. The NOAEL was 100 mg/kg feed, corresponding with 10 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.174 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:
8.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
96% bioavailability after oral administration (is already maximal)
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already applied in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.78 mg/m³
Most sensitive endpoint:
acute 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:
69.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key acute oral toxicity study available; no acute inhalation toxicity study available.
AF for dose response relationship:
1
Justification:
Various doses available; dose without effects considered as NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already applied in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties

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)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.086 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
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:
Key oral repeated dose toxicity study contained all necessary toxicological parameters (in contrast to dermal repeated dose toxicity study).
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.006 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
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:
0.05 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
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral repated dose toxicity study available
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for differences in duration of exposure:
2
Justification:
ECHA default for subchronic studies
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 mg/kg bw/day
Most sensitive endpoint:
acute 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:
80 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Various doses available; NOAEL clearly defined
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No other uncertainties

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Sources and info for the DNEL calculations:

In a key oral acute toxicity study in female rats dosed at 80, 125, 160, 200 and 320 mg/kg bw, Chloroacetamide had an LD50 of 138 mg/kg bw (Hoechst, 1976). Deadly poisoned animals (125, 160, 200 and 320 mg/kg bw) showed impaired balance, gasping breathing and bended posture; no macroscopically effects were observed. 80 m/kg bw was considered as NOAEL.

In a key 90 day oral repeated dose study (Hoechst, 1985) 80 Wistar rats (40 males and 40 females) were administered at doses of 0, 20, 100 and 500 mg Chloroacetamide/kg feed /day (equivalent to 0, 2, 10 and 50 mg/kg bw/day). In the high dose group, reduced body weight gain/food consumption and increased leucocytes were observed, as well as decreased liver weights in females, and smaller testes, reduced testicular weights, proliferation of Leydig cells and depression - standstill of spermiogenesis in males. After a 29 -day recovery period, partial to complete regeneration was observed in the testis, therefore this was considered to be reversible. The NOAEL was 100 mg/kg feed, corresponding with 10 mg/kg bw/day.

In a 30 day dermal repeated dose toxicity (Hoechst, 1967) chloroacetamide was tested without coverage in female rabbits at 25, 50, 100, 200 and 400 mg/kg bw /day (0.063, 0.13, 1.25, 0.50, 1.00 mL/kg bw/day). After the end of testing all surviving animals were observed for 3 days. In the 25 and 50 mg dose groups there were no findings. In the 100 mg dose group a slight body weight loss was observed during treatment and histological changes in liver, heart muscle and spleen. In the 200 mg dose group similar observations were done with a more significant weight loss. In the 400 mg dose group 3 animals died (1 on day 1, 2 and 3 respectively). Similar changes as in the 100 and 200 mg dose groups in liver, heart muscle and spleen were observed and a significant weight loss. In all dose groups there were local changes of the treated skin area (encrustation to induration). The dermal NOAEL was 50 mg/kg bw/day.

In a 13 weeks dermal toxicity repeated dose study, Konservierungsmittel CA 24 was applied to the shaved backs of male adult Wistar-rats, at doses of 12.5 and 50.0 mg/kg in Lanette (1 or 2%) or Aqua dest (2%). Neither test dependent or substance specific changes were observed in the growth parameters and histomorphological examinations. The dermal “no-effect” level of CA 24 in male adult rats is 50 mg/kg bw. Taking into account the 70% Chloroacetamide content and assuming that sodium benzoate was inactive on the skin, 35 mg act./kg bw was considered as local NOAEL. Based on the lower NOAEL, this was considered as key study. Considering a mean body weight of 300 g (based on study data) and a surface area of 325 cm2 (Derelanko, 2008; The Toxicologist's Pocket handbook p29), 10.5 mg was applied on 32.5 cm2 (10% body surface), corresponding to 0.32 mg/cm2. Compared to the rabbit NOAEL of 50 mg/kg bw and a mean body weight of 2.5 kg (based on study data) and a surface area of 1270 cm2 (Derelanko, 2008; The Toxicologist's Pocket handbook p29), 125 mg was applied on 127 cm2 (10% body surface), corresponding to 0.98 mg/cm2. Therefore the rat value was considered most conservative.

As the key 3-month dermal study (IBR, 1971; NOAEL = 50 mg/kg bw) did not have biochemistry and full histopathology, the NOAEL from the 90-day oral study was used as most conservative. In a key 90 day oral repeated dose study (Hoechst, 1985) 80 Wistar rats (40 males and 40 females) were administered at doses of 0, 20, 100 and 500 mg Chloroacetamide/kg feed /day (equivalent to 0, 2, 10 and 50 mg/kg bw/day). In the high dose group, reduced body weight gain/food consumption and increased leucocytes were observed, as well as decreased liver weights in females, and smaller testes, reduced testicular weights, proliferation of Leydig cells and depression - standstill of spermiogenesis in males. After a 29 -day recovery period, partial to complete regeneration was observed in the testis, therefore this was considered to be reversible. The NOAEL was 100 mg/kg feed, corresponding with 10 mg/kg bw/day.