Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 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):
125
Dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
83.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to QSAR (see separate IUCLID summary), the oral LOAEL was predicted as 68 mg/kg bw/day.

Modification of the dose descriptor occurs by applying the following correction factors to convert the relevant dose descriptor (in this case a LOAEL) into the correct starting point for DNEL calculation:

Correction factor for differences in bioavailability (ABS) for route-to route extrapolation = 0.5 (for an oral dose descriptor used to calculate an inhalation DNEL)

Correction factor for differences in respiratory volume = 0.38 m3/kg bw/ 8 h (for an oral dose descriptor from a rat study used to calculate an inhalation DNEL)

Correction factor for light activity at work = 0.67

Correction for differences between human and experimental exposure conditions = 1.4 (for an oral dose descriptor used to calculate an inhalation DNEL)

Therefore, for workers the LOAEC would be:

LOAEC = 68 * 1/0.38*0.5*0.67*1.4 = 83.9 mg/m3

AF for dose response relationship:
10
Justification:
Since the LOAEL is QSAR-derived, the maximum AF of 10 is applied to convert the LOAEC to a NOAEC and should therefore account for the fact that a very shallow dose response curve is assumed as a worst case in the absence of actual test data.
AF for differences in duration of exposure:
1
Justification:
Default for chronic studies (ECHA REACH Guidance)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling AF is needed because the final units are not mg/kg (ECHA REACH Guidance).
AF for other interspecies differences:
2.5
Justification:
Default (ECHA REACH Guidance)
AF for intraspecies differences:
5
Justification:
Default for workers (ECHA REACH Guidance)
AF for the quality of the whole database:
1
Justification:
Default (ECHA REACH Guidance)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.19 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):
500
Dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
95.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

According to QSAR (see separate IUCLID summary), the oral LOAEL was predicted as 68 mg/kg bw/day.

Modification of the dose descriptor occurs by applying the following correction factors to convert the relevant dose descriptor (in this case a LOAEL) into the correct starting point for DNEL calculation:

Correction factor for differences in bioavailability (ABS) for route-to route extrapolation = 1 (for an oral dose descriptor used to calculate a dermal DNEL)

Correction for differences between human and experimental exposure conditions = 1.4 (for an oral dose descriptor used to calculate a dermal DNEL)

Therefore, for workers the modified LOAEL would be:

LOAEL = 68 * 1*1.4 = 95.2 mg/kg bw/day

AF for dose response relationship:
10
Justification:
Since the LOAEL is QSAR-derived, the maximum AF of 10 is applied to convert the LOAEL to a NOAEL and should therefore account for the fact that a very shallow dose response curve is assumed as a worst case in the absence of actual test data.
AF for differences in duration of exposure:
1
Justification:
Default for chronic studies (ECHA REACH Guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (ECHA REACH Guidance)
AF for other interspecies differences:
2.5
Justification:
Default (ECHA REACH Guidance)
AF for intraspecies differences:
5
Justification:
Default for workers (ECHA REACH Guidance)
AF for the quality of the whole database:
1
Justification:
Default (ECHA REACH Guidance)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

All industrial activities involving the use of 4-aminobenzoyl-b-alanine will take place under strict Good Manufacturing Practices (GMP).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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):
250
Dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
29.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to QSAR (see separate IUCLID summary), the oral LOAEL was predicted as 68 mg/kg bw/day.

Modification of the dose descriptor occurs by applying the following correction factors to convert the relevant dose descriptor (in this case a LOAEL) into the correct starting point for DNEL calculation:

Correction factor for differences in bioavailability (ABS) for route-to route extrapolation = 0.5 (for an oral dose descriptor used to calculate an inhalation DNEL)

Correction factor for differences in respiratory volume = 1.15 m3/kg bw/ 8 h (for an oral dose descriptor from a rat study used to calculate an inhalation DNEL)

Correction for differences between human and experimental exposure conditions = 1 (for an oral dose descriptor used to calculate an inhalation DNEL)

Therefore, for the general population the LOAEC would be:

LOAEC = 68 * 1/1.15*0.5*1 = 29.6 mg/m3

AF for dose response relationship:
10
Justification:
Since the LOAEL is QSAR-derived, the maximum AF of 10 is applied to convert the LOAEC to a NOAEC and should therefore account for the fact that a very shallow dose response curve is assumed as a worst case in the absence of actual test data.
AF for differences in duration of exposure:
1
Justification:
Default for chronic studies (ECHA REACH Guidance)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling AF is needed because the final units are not mg/kg (ECHA REACH Guidance).
AF for other interspecies differences:
2.5
Justification:
Default (ECHA REACH Guidance)
AF for intraspecies differences:
10
Justification:
Default for the general population (ECHA REACH Guidance)
AF for the quality of the whole database:
1
Justification:
Default (ECHA REACH Guidance)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.07 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):
1 000
Dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

According to QSAR (see separate IUCLID summary), the oral LOAEL was predicted as 68 mg/kg bw/day.

Modification of the dose descriptor occurs by applying the following correction factors to convert the relevant dose descriptor (in this case a LOAEL) into the correct starting point for DNEL calculation:

Correction factor for differences in bioavailability (ABS) for route-to route extrapolation = 1 (for an oral dose descriptor used to calculate a dermal DNEL)

Correction for differences between human and experimental exposure conditions = 1 (for an oral dose descriptor used to calculate a dermal DNEL)

Therefore, for the general population the modified LOAEL would be:

LOAEL = 68 * 1*1 = 68 mg/kg bw/day

AF for dose response relationship:
10
Justification:
Since the LOAEL is QSAR-derived, the maximum AF of 10 is applied to convert the LOAEL to a NOAEL and should therefore account for the fact that a very shallow dose response curve is assumed as a worst case in the absence of actual test data.
AF for differences in duration of exposure:
1
Justification:
Default for chronic studies (ECHA REACH Guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (ECHA REACH Guidance)
AF for other interspecies differences:
2.5
Justification:
Default (ECHA REACH Guidance)
AF for intraspecies differences:
10
Justification:
Default for the general population (ECHA REACH Guidance)
AF for the quality of the whole database:
1
Justification:
Default (ECHA REACH Guidance)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 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):
1 000
Dose descriptor starting point:
LOAEL
Value:
68 mg/kg bw/day
AF for dose response relationship:
10
Justification:
Since the LOAEL is QSAR-derived, the maximum AF of 10 is applied to convert the LOAEL to a NOAEL and should therefore account for the fact that a very shallow dose response curve is assumed as a worst case in the absence of actual test data.
AF for differences in duration of exposure:
1
Justification:
Default for chronic studies (ECHA REACH Guidance)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (ECHA REACH Guidance)
AF for other interspecies differences:
2.5
Justification:
Default (ECHA REACH Guidance)
AF for intraspecies differences:
10
Justification:
Default for the general population (ECHA REACH Guidance)
AF for the quality of the whole database:
1
Justification:
Default (ECHA REACH Guidance)
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

Exposure of 4-aminobenzoyl-b-alanine to the general population will be negligible as it is an intermediate substance used in the synthesis of pharmaceutical ingredients. The intake of the pharmaceutical by the general public is not covered by REACH legislation.