Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.85 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
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:
0.24 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
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:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Kinetics (absorption figures for oral, dermal and inhalation route of exposure)

No data on absorption are available. 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. This approach will be taken forward to DNEL derivation. For dermal absorption the default ratio of 1 for oral to dermal absorption is used for DNEL derivation.

 

Acute toxicity

Tridecanamine, N-tridecyl-, branched and lineardoes not have to be classified for acute toxicity and therefore derivation of a acute DNEL is not necessary.

 

The substance is classified for corrosivity.The available data do not allow a quantitative approach. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent skin and eye corrosion.

 

Repeated dose toxicity

For the determination of the repeated dose toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed. In a GLP compliant 90 day oral gavage study according to OECD guideline 408 in male and female Wistar rats, the subchronic toxicity of tridecylamine, branched and linear was tested. The tested dose levels of 5, 15, and 45 mg/kg bw/day were selected based on the results of a 4-week range finding study that was conducted with 5 rats per sex and dose at 25, 50, and 75 mg/kg bw/day.

 

No changes were seen in animals treated with 5 mg/kg bw/day of tridecylamine, branched and linear. In the 15 mg/kg bw/day dose group, signs of toxicity included statistically significantly reduced body weights, body weight changes, and reduced food efficiency in males during the first 14 days of treatment, and respiration sounds and laboured respiration in 4/10 male and in 4/10 females starting from day 32 until the end of the study. Similar findings, but in higher frequency and severity were seen in the 45 mg/kg bw/day dose group. This dose also led to increased relative liver weights in females and was lethal for one male and one female rat. Sensimotor tests and reflexes were not affected by the treatment in any group except for the landing foot-splay test in high-dose males, probably due to the generally poor condition of these animals. Ophthalmological examinations revealed no substance-related effects. Clinical pathology, i.e. hematology, clinical chemistry, and urinalysis showed no treatment-related effects as compared to the control animals. Histopathological examinations revealed no changes beyond the normal.

 

Overall, signs of toxicity were seen in the 15 and 45 mg/kg bw/day dose groups. Therefore, the NOAEL for systemic toxicity was determined to be 5 mg/kg bw/day.

Mutagenicity

Tridecanamine, N-tridecyl-, branched and linearwasin vitronot mutagenic in the Ames, HPRT test, and chromosome aberration test.Therefore, tridecanamine, N-tridecyl-, branched and linear is considered to be non-mutagenic.

 

Reproduction toxicity

For the determination of the reproduction toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed.There was no specific fertility study withtridecylamine, branched and linearavailable, but in the GLP compliant 90 day oral gavage study performed according to OECD guideline 408 in male and female Wistar rats, effects on the male and female reproductive organs were examined in this study in terms of absolute and relative weight changes, histopathological, and functional changes of the male and female reproductive organs. Additionally, sperm parameters were determined on all animals with respect to sperm motility, sperm morphology, sperm head count (cauda epididymidis and testis). Estrous cycle was determined in all females from day 63 to 91. The tested dose levels were 5, 15, and 45 mg/kg bw/day

 

No weight changes were seen in the reproductive organs apart from a significantly decreased absolute weight of the testes. As this effect was only found in the mid-dose group, and not in the high-dose animals, it was considered to be not related to the administration of the test substance. This also holds true for the prolonged estrous cycle of the mid-dose females. As there was no dose relation observed, this finding was also considered not to be related to the treatment withtridecylamine, branched and linear. Sperm parameters were unchanged compared to controls. Thus, the NOAEL for the examined fertility parameters in males and females was 45 mg/kg bw/day, the highest dose tested.

 

Developmental toxicity

For the determination of the developmental toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed. Tridecylamine, branched and linearwas examined in a GLP compliant developmental/teratogenicity study according to OECD guideline 414 using pregnant female Wistar rats. Groups of 25 animals received dose levels of 0, 5, 20, or 80 mg/kg bw/day during days 6 through 19 of gestation (post coitum). The dams of the high dose group showed signs of toxicity as substantiated by a statistically significant impaired bodyweight gain and a corrected terminal body weight gain lowered by 21%. No significant clinical sign was noted in the other dose groups.

 

At scheduled necropsy, 22-24 animals/group had implantation sites. The conception rates reached 92% in all treated groups and were somewhat lower than in the control group (100%); this small decrease is not considered to be of any biological relevance. There were also no substance-related or biologically relevant differences between the groups with regard to mean number of corpora lutea and implantation sites, pre- and post-implantation losses, or the numbers of resorptions or viable fetuses.

 

The fetal weight and sex distribution was unchanged by the treatment. The occurrence of external malformations, skeletal and soft tissue malformations was comparable between the control and the treated test groups. A statistically significant increased incidence of some skeletal variations was, however, seen in fetuses from the high-dose females. The described findings are considered as skeletal variations because they also occur spontaneously in the strain of rats used and because they reflect a transient effect that is fully reversible postnatal. These were characterized as general delays in skeletal ossification (9.2% fetuses/litter vs. 0% in controls); incomplete ossification of supraoccipital (28.6% fetuses/litter vs. 16.5% in controls); bipartite ossification of the thoracic centrum (4.2% fetuses/litter vs. 0% in controls); incomplete ossification of the sacral arch (57.4% fetuses/litter vs. 25.7% in controls). The overall incidence of skeletal variations was not different from historical control data.

 

There were no signs of teratogenicity noted at any dose level. In summary, there were slight indications of substance-induced effects on skeletal maturation without effects on fetal weight at a maternally toxic dose of 80 mg/kg bw/day. Gestational parameters were unaffected up to and including 80 mg/kg bw/day. Fetal parameters were unaffected at all dose levels except the increased occurrence of transient delays in the ossification of the skull and the ventral column in the high dose group. The overall incidence of skeletal variations was not different from historical control data.

 

Therefore, it was concluded that the NOAEL for maternal toxicity and for prenatal development was 20 mg/kg bw/day in this study. There was no sign of teratogenicity at the highest tested dose of 80 mg/kg bw/day.

DNEL derivation

For short-term toxicity, no DNEL needs to be derived for all routes of exposure.

 

For long-term toxicity, regarding systemic effects, a NOAEL of 5 mg/kg bw/day was observed for male and female rats inasubchronic gavage dose toxicity study and will be used for the DNEL derivation.Long-term dermal and inhalation toxicity data is not available and therefore route-to-route extrapolation will be performed.

 

According to the Guidance on the Application of Regulation (EC) No 1272/2008, when a substance is present in concentrations of less than 5% the preparation is not considered corrosive to skin. In case concentrations are between 1% and 5% classification for skin irritation is applicable.

Worker DNELs

 

Long-term –inhalation, systemic effects(based on a subchronic study with tridecylamine, branched and linear)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 5 mg/kg bw/day

Step 2) Modification of starting point

0.52

 

 

 

 

2

 

 

 

0.38 m3/kg bw

 

 

 

6.7 m3/10 m3

Correction for the difference in weight of tridecanamine, N-tridecyl-, branched and linear (381.75 g/mol) andtridecylamine, branched and linear (199.38 g/mol).

                    

Default factor for oral to inhalation route to route extrapolation, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Modified dose-descriptor

5 x 6.7 / (0.52 x 2 x 0.38 x 10) = 8.48 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.

Intraspecies

5

Default assessment factor

Exposure duration

2

Subchronic to chronic extrapolation

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

8.48 / (1 x 5 x 2 x 1 x 1) =0.85mg/m3

 

For non-corrosive concentrations oftridecanamine, N-tridecyl-, branched and linear, the following dermal DNEL has been derived:

Long-term – dermal, systemic effects(based on a subchronic study with tridecylamine, branched and linear)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 5 mg/kg bw/day

Step 2) Modification of starting point

0.52

 

 

 

 

1

Correction for the difference in weight of tridecanamine, N-tridecyl-, branched and linear (381.75 g/mol) and tridecylamine, branched and linear (199.38 g/mol).

 

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation.

Modified dose-descriptor

5 / 0.52 = 9.6 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling

Intraspecies

5

Default assessment factor

Exposure duration

2

Subchronic to chronic extrapolation

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

9.6 / (4 x 5 x 2 x 1 x 1) =0.24 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
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:
DNEL (Derived No Effect Level)
Value:
0.12 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
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:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Kinetics (absorption figures for oral, dermal and inhalation route of exposure)

No data on absorption are available. 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. This approach will be taken forward to DNEL derivation. For dermal absorption the default ratio of 1 for oral to dermal absorption is used for DNEL derivation.

 

Acute toxicity

Tridecanamine, N-tridecyl-, branched and lineardoes not have to be classified for acute toxicity and therefore derivation of a acute DNEL is not necessary.

 

The substance is classified for corrosivity.The available data do not allow a quantitative approach. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent skin and eye corrosion.

 

Repeated dose toxicity

For the determination of the repeated dose toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed. In a GLP compliant 90 day oral gavage study according to OECD guideline 408 in male and female Wistar rats, the subchronic toxicity of tridecylamine, branched and linear was tested. The tested dose levels of 5, 15, and 45 mg/kg bw/day were selected based on the results of a 4-week range finding study that was conducted with 5 rats per sex and dose at 25, 50, and 75 mg/kg bw/day.

 

No changes were seen in animals treated with 5 mg/kg bw/day of tridecylamine, branched and linear. In the 15 mg/kg bw/day dose group, signs of toxicity included statistically significantly reduced body weights, body weight changes, and reduced food efficiency in males during the first 14 days of treatment, and respiration sounds and laboured respiration in 4/10 male and in 4/10 females starting from day 32 until the end of the study. Similar findings, but in higher frequency and severity were seen in the 45 mg/kg bw/day dose group. This dose also led to increased relative liver weights in females and was lethal for one male and one female rat. Sensimotor tests and reflexes were not affected by the treatment in any group except for the landing foot-splay test in high-dose males, probably due to the generally poor condition of these animals. Ophthalmological examinations revealed no substance-related effects. Clinical pathology, i.e. hematology, clinical chemistry, and urinalysis showed no treatment-related effects as compared to the control animals. Histopathological examinations revealed no changes beyond the normal.

 

Overall, signs of toxicity were seen in the 15 and 45 mg/kg bw/day dose groups. Therefore, the NOAEL for systemic toxicity was determined to be 5 mg/kg bw/day.

Mutagenicity

Tridecanamine, N-tridecyl-, branched and linearwasin vitronot mutagenic in the Ames, HPRT test, and chromosome aberration test.Therefore, tridecanamine, N-tridecyl-, branched and linear is considered to be non-mutagenic.

 

Reproduction toxicity

For the determination of the reproduction toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed.There was no specific fertility study withtridecylamine, branched and linearavailable, but in the GLP compliant 90 day oral gavage study performed according to OECD guideline 408 in male and female Wistar rats, effects on the male and female reproductive organs were examined in this study in terms of absolute and relative weight changes, histopathological, and functional changes of the male and female reproductive organs. Additionally, sperm parameters were determined on all animals with respect to sperm motility, sperm morphology, sperm head count (cauda epididymidis and testis). Estrous cycle was determined in all females from day 63 to 91. The tested dose levels were 5, 15, and 45 mg/kg bw/day

 

No weight changes were seen in the reproductive organs apart from a significantly decreased absolute weight of the testes. As this effect was only found in the mid-dose group, and not in the high-dose animals, it was considered to be not related to the administration of the test substance. This also holds true for the prolonged estrous cycle of the mid-dose females. As there was no dose relation observed, this finding was also considered not to be related to the treatment withtridecylamine, branched and linear. Sperm parameters were unchanged compared to controls. Thus, the NOAEL for the examined fertility parameters in males and females was 45 mg/kg bw/day, the highest dose tested.

 

Developmental toxicity

For the determination of the developmental toxicity of , tridecanamine, N-tridecyl-, branched and linearread-across with tridecylamine, branched and linear was performed. Tridecylamine, branched and linearwas examined in a GLP compliant developmental/teratogenicity study according to OECD guideline 414 using pregnant female Wistar rats. Groups of 25 animals received dose levels of 0, 5, 20, or 80 mg/kg bw/day during days 6 through 19 of gestation (post coitum). The dams of the high dose group showed signs of toxicity as substantiated by a statistically significant impaired bodyweight gain and a corrected terminal body weight gain lowered by 21%. No significant clinical sign was noted in the other dose groups.

 

At scheduled necropsy, 22-24 animals/group had implantation sites. The conception rates reached 92% in all treated groups and were somewhat lower than in the control group (100%); this small decrease is not considered to be of any biological relevance. There were also no substance-related or biologically relevant differences between the groups with regard to mean number of corpora lutea and implantation sites, pre- and post-implantation losses, or the numbers of resorptions or viable fetuses.

 

The fetal weight and sex distribution was unchanged by the treatment. The occurrence of external malformations, skeletal and soft tissue malformations was comparable between the control and the treated test groups. A statistically significant increased incidence of some skeletal variations was, however, seen in fetuses from the high-dose females. The described findings are considered as skeletal variations because they also occur spontaneously in the strain of rats used and because they reflect a transient effect that is fully reversible postnatal. These were characterized as general delays in skeletal ossification (9.2% fetuses/litter vs. 0% in controls); incomplete ossification of supraoccipital (28.6% fetuses/litter vs. 16.5% in controls); bipartite ossification of the thoracic centrum (4.2% fetuses/litter vs. 0% in controls); incomplete ossification of the sacral arch (57.4% fetuses/litter vs. 25.7% in controls). The overall incidence of skeletal variations was not different from historical control data.

 

There were no signs of teratogenicity noted at any dose level. In summary, there were slight indications of substance-induced effects on skeletal maturation without effects on fetal weight at a maternally toxic dose of 80 mg/kg bw/day. Gestational parameters were unaffected up to and including 80 mg/kg bw/day. Fetal parameters were unaffected at all dose levels except the increased occurrence of transient delays in the ossification of the skull and the ventral column in the high dose group. The overall incidence of skeletal variations was not different from historical control data.

 

Therefore, it was concluded that the NOAEL for maternal toxicity and for prenatal development was 20 mg/kg bw/day in this study. There was no sign of teratogenicity at the highest tested dose of 80 mg/kg bw/day.

DNEL derivation

For short-term toxicity, no DNEL needs to be derived for all routes of exposure.

 

For long-term toxicity, regarding systemic effects, a NOAEL of 5 mg/kg bw/day was observed for male and female rats inasubchronic gavage dose toxicity study and will be used for the DNEL derivation.Long-term dermal and inhalation toxicity data is not available and therefore route-to-route extrapolation will be performed.

 

According to the Guidance on the Application of Regulation (EC) No 1272/2008, when a substance is present in concentrations of less than 5% the preparation is not considered corrosive to skin. In case concentrations are between 1% and 5% classification for skin irritation is applicable.

General population DNELs

 

Long-term – oral, systemic effects (based on a subchronic study with tridecylamine, branched and linear)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 5 mg/kg bw/day

Step 2) Modification of starting point

0.52

Correction for the difference in weight of tridecanamine, N-tridecyl-, branched and linear (381.75 g/mol) and tridecylamine, branched and linear (199.38 g/mol).

Modified dose-descriptor

5 / 0.52 = 9.6 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling.

Intraspecies

10

Default assessment factor

Exposure duration

2

Subchronic to chronic extrapolation

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

9.6 / (4 x 10 x 2 x 1 x 1) =0.12 mg/kg bw/day

 

 

Long-term – inhalation, systemic effects (based on a subchronic study with tridecylamine, branched and linear)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 5 mg/kg bw/day

 

Step 2) Modification of starting point

0.52

 

 

 

 

2

 

 

 

1.15 m3/kg bw

 

 

Correction for the difference in weight of tridecanamine, N-tridecyl-, branched and linear (381.75 g/mol) and tridecylamine, branched and linear (199.38 g/mol).

 

Default factor for oral to inhalation route to route extrapolation, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)

Modified dose-descriptor

5 / (0.52 x 2 x 1.15) = 4.18 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.

Intraspecies

10

Default assessment factor

Exposure duration

2

Subchronic to chronic extrapolation

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

4.18 / (1 x 10 x 2 x 1 x 1) =0.21mg/m3

  

For non-corrosive concentrations oftridecanamine, N-tridecyl-, branched and linear, the following dermal DNEL has been derived:

 

Long-term – dermal, systemic effects (based on a subchronic study with tridecylamine, branched and linear)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 5 mg/kg bw/day

 

Step 2) Modification of starting point

0.52

 

 

 

 

1

Correction for the difference in weight of tridecanamine, N-tridecyl-, branched and linear (381.75 g/mol) andtridecylamine, branched and linear (199.38 g/mol).

 

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation.

Modified dose-descriptor

5 / 0.52 = 9.6 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4

Assessment factor for allometric scaling.

Intraspecies

10

Default assessment factor

Exposure duration

2

Subchronic to chronic extrapolation

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

9.6 / (4 x 10 x 2 x 1 x 1) =0.12 mg/kg bw/day