Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.357 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AOEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEC
DNEL value:
35.7 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:
No correction needed (based on NOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I inclusion revision of Chapter 4, 2009
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
2
Justification:
Reproductive data from read across substances
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
4.29 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AOEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
LOAEC
DNEL value:
536 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:
5
Justification:
The clinical signs seen at LOAEL indicated bad condition, but no moribundity. Therefore factor 5 was selected.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

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:
other toxicological threshold
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AOEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available.
AF for dose response relationship:
1
Justification:
No correction needed (based on NOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
2
Justification:
Reproductive data from read across substances
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
13.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: AOEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
LOAEL
DNEL value:
4 000 mg/kg bw/day
AF for dose response relationship:
3
Justification:
The clinical signs at LOAEL only included crust formation. Therefore factor 3 was selected.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Default factor according to TNsG on Annex I
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.373 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: AOEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
75
Dose descriptor starting point:
other: LOAEL
AF for dose response relationship:
3
Justification:
The clinical signs at LOAEL only included crust formation. Therefore factor 3 was selected.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applicable for local effects.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

In a key oral toxicity study (Dvorakova, 2006a), Chloramin B trihydrate was administered by gavage in a single dose as solution in water for injection to three groups of three female Wistar rats: group No. 1 (first step) 2000 mg/kg bw, group No. 2 (second step) 300 mg/kg bw and group No. 3 (third step) 300 mg/kg bw. The test substance administered at the dose of 2000 mg/kg bw caused death of all three animals, clinical signs of intoxication were observed in all three animals and macroscopic changes were diagnosed during pathological examination in all three animals. The test substance administered at the dose of 300 mg/kg bw caused no death in females, very mild clinical signs of intoxication were observed in three animals (erected hair, hunched posture) and macroscopic changes were diagnosed during pathological examination in three females. According to the study results the value of LD50 of the test substance Chloramin B trihydrate for rats is in the range >300 mg/kg bw to ≤ 2000 mg/kg bw. The exact value was not given in the report, but can be considered to be around 1150 mg/kg bw. The dose of 300 mg/kg bw can be considered as the LOAEL based on clinical findings seen.

The oral administration of Chloramin B trihydrate to rats by gavage for period of 90 consecutive days at dose levels 20, 60, 180 mg/kg bw/day produced no significant changes in functional observations, ophthalmological examination and did not cause mortality. Overall assessment of results showed, that the test substance, after 90-day oral application caused reversible decrease in body weight increments in both sexes (more marked in males) in all dose levels. It was connected with reversible decrease of food consumption and food conversion in both sexes. Reversible changes of health status (piloerection) and clinical changes immediately after application (excited behavior) were recorded in both sexes of the highest dose level. Haematological examination showed an effect on leukocyte differential count in both sexes without dependence on dose level. Portion of lymphocytes was increased and portion of monocytes and granulocytes was decreased. In females of the highest dose level also the increase of number of leukocytes and platelets was observed. During biochemical examination of blood the statistically significant changes were detected at the highest dose level: increased value of urea in both sexes, increased value of chloride ions in males, decreased value of AST, creatinine and potassium ions in males, increased value of bilirubin and ALT in females and decreased value of creatinine and sodium ions in females. Increase of bilirubin was irreversible. Statistically significantly decreased volume of urine was detected in males especially at highest dose level. It was connected with increase of specific gravity of urine. Increased value of pH of urine was recorded in satellite males of the dose level 180 mg/kg bw/day and females of the dose levels 60 and 180 mg/kg bw/day. Decreased volume of urine accompanied by higher specific gravity of urine occurred also in females of the dose level 180 mg/kg bw/day. The most important histological affections were diagnosed in kidneys of males of the highest dose level –hyaline droplets in renal tubules and mesangial cell proliferation in renal glomeruli. In the same treated group also the increase of incidence of histiocytosis of lymph nodes and involution of thymus was registered. In females the increased incidence of hydrometra of uterus was found out in all treated groups irrespective of dose level.

The LOAEL (Lowest Observed Adverse Effect Level) for males and females was established as 60 mg/kg bw/day. The NOAEL (No Observed Adverse Effect Level) for males and females is 20 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.174 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.4 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:
No correction needed (based on NOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
2
Justification:
Reproductive data from read across substances
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
2.09 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
125
Modified dose descriptor starting point:
LOAEC
DNEL value:
261 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:
5
Justification:
The clinical signs at LOAEL indicated bad condition, but no moribundity. Therefore factor 5 was selected.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already applied in route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

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:
other toxicological threshold
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available.
AF for dose response relationship:
1
Justification:
No correction needed (based on NOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
2
Justification:
Reproductive data from read across substances
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
13.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
LOAEL
DNEL value:
4 000 mg/kg bw/day
AF for dose response relationship:
3
Justification:
The clinical signs at LOAEL only included crust formation. Therefore factor 3 was selected.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.373 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
75
Dose descriptor starting point:
other: LOAEL
AF for dose response relationship:
3
Justification:
The clinical signs at LOAEL only included crust formation. Therefore factor 3 was selected.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applicable for local effects.
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.05 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No correction needed (based on NOAEL)
AF for differences in duration of exposure:
2
Justification:
Assessment from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
2
Justification:
Reproductive data from read across substances
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: AEL according to Directive 98/8/EC - TNsG on Annex I Inclusion - Revision of Chapter 4.1: Quantitative Human Health Risk Characterisation 2009
Overall assessment factor (AF):
500
Modified dose descriptor starting point:
LOAEL
DNEL value:
300 mg/kg bw/day
AF for dose response relationship:
5
Justification:
The clinical signs at LOAEL indicated bad condition, but no moribundity. Therefore factor 5 was selected.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to TNsG on Annex I
AF for other interspecies differences:
2.5
Justification:
Remaining differences between species
AF for intraspecies differences:
10
Justification:
Default factor according to TNsG on Annex I
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No indication that an additional factor is needed.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

In a key oral toxicity study (Dvorakova, 2006a), Chloramin B trihydrate was administered by gavage in a single dose as solution in water for injection to three groups of three female Wistar rats: group No. 1 (first step) 2000 mg/kg bw, group No. 2 (second step)300 mg/kg bw and group No. 3 (third step) 300 mg/kg bw. The test substance administered at the dose of 2000 mg/kg bw caused death of all three animals, clinical signs of intoxication were observed in all three animals and macroscopic changes were diagnosed during pathological examination in all three animals. The test substance administered at the dose of 300 mg/kg bw caused no death in females, very mild clinical signs of intoxication were observed in three animals (erected hair, hunched posture) and macroscopic changes were diagnosed during pathological examination in three females. According to the study results the value of LD50 of the test substance Chloramin B trihydrate for rats is in the range >300 mg/kg bw to ≤ 2000 mg/kg bw. The exact value was not given in the report, but can be considered to be around 1150 mg/kg bw. The dose of 300 mg/kg bw can be considered as the LOAEL based on clinical findings seen.

The oral administration of Chloramin B trihydrate to rats by gavage for period of 90 consecutive days at dose levels 20, 60, 180 mg/kg bw/day produced no significant changes in functional observations, ophthalmological examination and did not cause mortality. Overall assessment of results showed, that the test substance, after 90-day oral application caused reversible decrease in body weight increments in both sexes (more marked in males) in all dose levels. It was connected with reversible decrease of food consumption and food conversion in both sexes. Reversible changes of health status (piloerection) and clinical changes immediately after application (excited behavior) were recorded in both sexes of the highest dose level. Haematological examination showed an effect on leukocyte differential count in both sexes without dependence on dose level. Portion of lymphocytes was increased and portion of monocytes and granulocytes was decreased. In females of the highest dose level also the increase of number of leucocytes and platelets was observed. During biochemical examination of blood the statistically significant changes were detected at the highest dose level: increased value of urea in both sexes, increased value of chloride ions in males, decreased value of AST, creatinine and potassium ions in males, increased value of bilirubin and ALT in females and decreased value of creatinine and sodium ions in females. Increase of bilirubin was irreversible. Statistically significantly decreased volume of urine was detected in males especially at highest dose level. It was connected with increase of specific gravity of urine. Increased value of pH of urine was recorded in satellite males of the dose level 180 mg/kg bw/day and females of the dose levels 60 and 180 mg/kg bw/day. Decreased volume of urine accompanied by higher specific gravity of urine occurred also in females of the dose level 180 mg/kg bw/day. The most important histological affections were diagnosed in kidneys of males of the highest dose level –hyaline droplets in renal tubules and mesangial cell proliferation in renal glomeruli. In the same treated group also the increase of incidence of histiocytosis of lymph nodes and involution of thymus was registered. In females the increased incidence of hydrometra of uterus was found out in all treated groups irrespective of dose level.

The LOAEL (Lowest Observed Adverse Effect Level) for males and females was established as 60 mg/kg bw/day. The NOAEL (No Observed Adverse Effect Level) for males and females is 20 mg/kg bw/day.