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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.36 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
0.89 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.44 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the dog in 8 h corresponds to 0.1344 m3/kg bw, additional correction for the higher standard respiratory volumes of workers compared to resting persons: correction factor = (1 ÷ 0.1344) * (6.7 ÷ 10) = 4.99

Overall correction factor: 4.99

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
Chronic study – no time extrapolation required
AF for interspecies differences (allometric scaling):
1
Justification:
Default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default AF for intraspecies differences (worker)
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to regulatory standards and adequately reported.
AF for remaining uncertainties:
1
Justification:
No uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long 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:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor starting point:
other: NOEL
Value:
360 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of starting point necessary as dermal study was used.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
2.4
Justification:
Standard value for rabbits
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
high hazard (no threshold derived)

Additional information - workers

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: NOEL of 250 mg chlorhexidine diacetate/kg bw/d (corresponding to 360 mg chlorhexidine digluconate) in male and female NZW rabbits in a 13 week dermal study (Henwood, 1988)

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 5 (worker)

Time extrapolation: 2 (subchronic study)

Route to route extrapolation: no correction necessary

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.4 * 2.5 * 5 * 2 = 60

DNEL long-term– dermal, systemic effects: 360 mg/kg bw/d ÷ 60 = 6 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 0.89 mg/kg bw/d for systemic effects in a chronic dog study.

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the rat in 8 h corresponds to 0.1344 m3/kg bw, additional correction for the higher standard respiratory volumes of workers compared to resting persons: correction factor = (1 ÷ 0.1344) * (6.7 ÷ 10) = 4.99

Overall correction factor: 4.99

Corrected starting point: 0.89 * 4.99 = 4.44 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.5 (remaining differences)

Intraspecies: 5 (worker)

Time extrapolation: no correction necessary

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.5 * 5 = 12.5

DNEL Long-term–inhalation, systemic effects: 4.44 mg/m3 ÷ 12.5 = 0.36 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 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
Dose descriptor starting point:
NOAEL
Value:
0.89 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2.21 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the dog in 24 h corresponds to 0.4032 m3/kg bw, correction factor 1 ÷ 0.4032 = 2.48

Overall correction factor: 2.48

Corrected starting point: 0.89 * 2.48 = 2.21 mg/m3

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
Chronic study – no time extrapolation required
AF for interspecies differences (allometric scaling):
1
Justification:
Default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default AF for intraspecies differences (general population)
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to regulatory standards and adequately reported.
AF for remaining uncertainties:
1
Justification:
No uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - 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:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Dose descriptor starting point:
other: NOEL
Value:
360 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of starting point necessary as dermal study was used.

AF for dose response relationship:
1
Justification:
no correction necessary
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
2.4
Justification:
rabbits
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no correction necessary
AF for remaining uncertainties:
1
Justification:
no correction necessary
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:
0.03 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):
35
Dose descriptor starting point:
NOAEL
Value:
0.89 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification necessary as oral study was used

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
Chronic study – no time extrapolation required
AF for interspecies differences (allometric scaling):
1.4
Justification:
Allometric scaling dog to humans.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default AF for intraspecies differences (general population)
AF for the quality of the whole database:
1
Justification:
no correction necessary
AF for remaining uncertainties:
1
Justification:
no correction necessary
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
1 000
Dose descriptor starting point:
other: LD50
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

LD50 value of >= 2000 mg/kg in rats

AF for dose response relationship:
10
Justification:
LD50 to NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
see below "other interspecies differences"
AF for other interspecies differences:
10
Justification:
Standard factor of 10 is used
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no correction necessary
AF for remaining uncertainties:
1
Justification:
no correction necessary

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

DNEL Acute Short-term - oral, systemic effects

Relevant dose descriptor for the endpoint concerned: LD50 value of >= 2000 mg/kg in rats

Assessment factors relating to the extrapolation procedure:

Interspecies: 10

Intraspecies: 10

Additional safety factor: 10 (LD50 to NOAEL)

Overall assessment factor: 10 * 10 * 10 = 1000

DNEL Acute Short-term - dermal, systemic effects: 2000 ÷ 1000 = 2 mg/kg bw/d

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: NOEL of 250 mg chlorhexidine diacetate/kg bw/d (corresponding to 360 mg chlorhexidine digluconate) in male and female NZW rabbits in a 13 week dermal study (Henwood, 1988)

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: 2 (subchronic study)

Route to route extrapolation: no correction necessary

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.4 * 2.5 * 10 * 2 = 120

DNEL long-term– dermal, systemic effects: 360 mg/kg bw/d ÷ 120 = 3 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 0.89 mg/kg bw/d in a chronic study with dogs.

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the dog in 24 h corresponds to 0.4032 m3/kg bw, correction factor 1 ÷ 0.4032 = 2.48

Overall correction factor: 2.48

Corrected starting point: 0.89 * 2.48 = 2.21 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: no correction necessary

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.5 * 10 = 25

DNEL Long-term–inhalation, systemic effects: 2.21 mg/m3 ÷ 25 = 0.09 mg/m3

DNEL Long-term - oral, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 0.89 mg/kg bw/d in a chronic study with dogs.

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure: similar to general population (no correction necessary)

Exposure conditions: oral uptake via food in humans compared to application via diet (no correction necessary)

Assessment factors relating to the extrapolation procedure:

Interspecies: 1.4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: no correction necessary

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 1.4 * 2.5 * 10 = 35

DNEL long-term– dermal, systemic effects: 0.89 mg/kg bw/d ÷ 35 = 0.03 mg/kg bw/d