Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 274-159-1 | CAS number: 69852-45-5
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.32 mg/m³
- 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:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 132.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The reproductive toxicity of 3-[[3-(dimethylamino)propyl]amino]propiononitrile was determined using a 2 -generation test design that pre-dates current OECD guidelines but following interpretation the study provided adequate data for use. The NOAEL was determined to be 150 mg/kg bw day, this was also the maximum tested dose.
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:
- 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 intraspecies 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.
- Justification:
- The database is considered to be of good and there is no need to include an assessment factor.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 17.6 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):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 881.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The acute oral toxicity to the rat was assessed over a 14 -day period, Animals were dosed at 1000, 2150, 2780, 3170, 3590 and 4640 mg/kg bw d. Mortalities occured at doses >1000 mg/kg bw day and the LD50 was determined to be 2284 mg/kg bw/d. Due to a lack of effects at 1000 mg/kg bw day this dose has been used to derive DNEL values for acute/short term exposure.
An toxicity study by the inhalation is not available so 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.
1000/2 (absorption rate) / 0.38 m3/kg bw = Inhalation NOAEL Rat of 1315.8 mg/m3 (8h)
1315.8 x 0.67 = 881.6 mg/m3
- Justification:
- Assessment factor for dose response is not required, the NOAEL from a 14-day acute study has been used for derivation of the DNEL/NOAEC. The acute laboratoiy endpoint is considered to reflect the most appropriate endpoint for assessing acute risk.
- 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:
- 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 intraspecies 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.
- Justification:
- The database is considered to be of good and there is no need to include an assessment factor.
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3 mg/kg bw/day
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The acute dermal LD50 of TK 12271 in rats of both sexes observed over a period of 14 days is greater than 4000 mg/kg, The test material has therefore practically no acute toxicity to the rat by this route of application. Skin irritation was also no observed. As a ong term dermal toxicity study is not available the oral reproductive toxicity endpoint determined using a 2 -generation test design will be used for assessment purposes. The NOAEL was determined to be 150 mg/kg bw day, this was also the maximum tested dose.
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. However, based on the log Kow of 0.492 and molecular weight of the substance (155.24), the skin permeability according to Fitzpatrick et al (2004) of the substance is considered to be slightly permeable to the skin based on a calculated Log skin permeation coefficient of -4.18. Therefore, a ratio of 0.5 for oral to dermal absorption is provisonally suggested for DNEL derivation.
Modified dose descriptor (dermal) = 150/0.5 (skin absorption rate for slightly permeable substance) = 300 mg/kg bw
- AF for differences in duration of exposure:
- 2
- 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:
- 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 intraspecies 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.
- Justification:
- The database is considered to be of good and there is no need to include an assessment factor
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Explanation for the modification of the dose descriptor starting point:
The results of three acute (14-day) dermal tests indicated that slight irritation accured at concentrations >4000 mg/kg bw day based on the professional use pattern of the substance acute exposure to high concentrations is unlikely and therefore the risk management measures enforced based on the long term DNEL are considered adequate for protection against acute hazard/exposure.
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.
Short-term toxicity:
According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, acute DNELs should default to the long term systemic DNELs.
For local effects, a DNEL was not quantifiable; however, as the substance is classified as Cat 1 for eye damage and as Cat 2 skin irritant and, local effects must be assessed qualitatively and risk management measures applied as necessary. The potential for respiratory sensitization is unknown; however, given its skin sensitization potential, this endpoint also is assessed qualitatively.
Long-term toxicity:
A two-generation reproduction study is available. A NOAEL of 150 mg/kg bw was determined this was the maximum tested concentration and used to derive the DNEL.
Since only a sub-chronic toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. 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-to-inhalation extrapolation. On the assumption that, in general, dermal absorption will not be higher than oral absorption, 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. However, based on the log Kow of 0.492 and molecular weight of the substance (155.24), the skin permeability according to Fitzpatrick et al (2004) of the substance is considered to be slightly permeable to the skin. Therefore, a ratio of 0.5 for oral to dermal absorption is provisonally suggested for DNEL derivation
General Population - Hazard via inhalation 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
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
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
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
