Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.019 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
2.85 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1.91 mg/m³
Explanation for the modification of the dose descriptor starting point:

The toxicity of 1,3-Benzenedimethanamine, reaction products with glycidyl tolyl was investigated with the Reproduction/ Developmental Toxicity Screening Test” (adopted 22 March 1996). This study was also designed to be compatible with Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 15 mg/kg bw/day. The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 25 mg/kg bw/day.

Since only a sub-chronic oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation routes. According to Chapter R.8 of REACH Guidance on information

requirements and chemical safety assessment, it is proposed in the absence of route specific information on the starting route, to include a default factor of 2 in the case of oral-inhalation extrapolation. On the assumption, that in general, dermal absorption will not be higher than oral absorption, no default factor is introduced for the oral to dermal extrapolation. The REACH Guidance on information requirements and chemical safety assessment
(R.8.4.2) prescribes a default factor of 1 in case of oral to dermal extrapolation. This approach will be taken forward to DNEL derivation.

15/2 (absorption rate) / 0.38 m3/kg bw = Inhalation NOAEL Rat of 2.85 mg/m3 (8h)

NOAEC = 2.85 x 0.67 = 1.91 mg/m3)

AF for differences in duration of exposure:
2
Justification:
Assessment factor of two included due to extrapolation from a sub-chronic to chronic endpoint
AF for interspecies differences (allometric scaling):
2.5
Justification:
Default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e.toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). As described in R.8.4.3.1 Assessment factors relating to the extrapolation procedure of the REACH Guidance)
AF for other interspecies differences:
5
Justification:
For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for intraspecies differences:
4
Justification:
Assuming body weight of rat 0.250 kg an allometric scaling factor of 4 is applied based on the assumed Human weight of 70 kg (as detailed in Table R8-3 of REACH Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Study conducted to GLP Standards and international OECD guidelines
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The toxicity of 1,3-Benzenedimethanamine, reaction products with glycidyl tolyl was investigated with the Reproduction/ Developmental Toxicity Screening Test” (adopted 22 March 1996). This study was also designed to be compatible with Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 15 mg/kg bw/day. The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 25 mg/kg bw/day.

Since only a sub-chronic oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation routes. According to Chapter R.8 of REACH Guidance on information

requirements and chemical safety assessment, it is proposed in the absence of route specific information on the starting route, to include a default factor of 2 in the case of oral-inhalation extrapolation. On the assumption, that in general, dermal absorption will not be higher than oral absorption, no default factor is introduced for the oral to dermal extrapolation. The REACH Guidance on information requirements and chemical safety assessment
(R.8.4.2) prescribes a default factor of 1 in case of oral to dermal extrapolation. This approach will be taken forward to DNEL derivation.

AF for differences in duration of exposure:
2
Justification:
Assessment factor of two included due to extrapolation from a sub-chronic to chronic endpoint)
AF for interspecies differences (allometric scaling):
2.5
Justification:
Default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). As described in R.8.4.3.1 Assessment factors relating to the extrapolation procedure of the REACH Guidance)
AF for other interspecies differences:
5
Justification:
For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for intraspecies differences:
4
Justification:
Assuming body weight of rat 0.250 kg an allometric scaling factor of 4 is applied based on the assumed Human weight of 70 kg (as detailed in Table R8-3 of REACH Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Study conducted to GLP Standards and international OECD guidelines
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information
Explanation for the modification of the dose descriptor starting point:

1,3 -Benzenedimethanamine, reaction products with glycidyl tolyl is classified as a Cat 1 sensitizer, as a consequence and in accordance with Part E Table E.3 -1 of the ECHA guidance the registered substance is allocated to the High Hazard band and qualitative assessment will be required as it is not possible to derive a threshold dose for sensitization.

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

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:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The substance is not intended to be marketed for consumer use.